The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate.
With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells.
Giglio
M J
MJ
Department of Physiology, University of Buenos Aires, Faculty of Dentistry, Argentina.
Brandan
N
N
Leal
T L
TL
Bozzini
C E
CE
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007275:Injections, Intravenous; D007504:Iron Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014501:Uranium / Q000633:toxicity*; D014502:Uranyl Nitrate / Q000633:toxicity*
D007504:Iron Radioisotopes; D014502:Uranyl Nitrate; D004921:Erythropoietin; D014501:Uranium