title: Evaluation of the erythroid regenerative response in two different models of experimentally induced iron deficiency anemia.
abstract: Anemia was induced in weanling Sprague Dawley rats either by feeding an iron-deficient diet or by chronic phlebotomy. The erythroid regenerative response was then evaluated before and after a hemolytic event, and results were compared with those of a third group of control nonphlebotomized rats fed an iron-replete diet. Diet and phlebotomy groups developed a similar degree of anemia (mean hemoglobin concentration 7.9 g/dL and 7.8 g/dL, respectively; controls, 13.9 g/dL) and hypoferremia (mean serum iron concentration 25.4 microgram/dL and 34.9 microgram/dL, respectively; controls, 222.0 microgram/dL). However, the anemia in diet rats was nonregenerative (reticulocyte count, 83.1 X 10(3) cells/microliter) and associated with bone marrow erythroid hypoplasia; whereas the anemia in phlebotomy rats was regenerative (reticulocyte count, 169.6 X 10(3) cells/microliter) and associated with bone marrow erythroid hyperplasia. Thrombocytosis was seen in diet rats (1,580 X 10(3) cells/microliter) but not phlebotomy rats (901 X 10(3) cells/microliter) when compared with controls (809 X 10(3) cells/microliter). To further evaluate the regenerative capability, phenylhydrazine (PHZ) was administered to induce hemolysis. Erythrocyte mass declined approximately 25% in all groups, including controls. The reticulocytosis (265.3 X 10(3) cells/microliter) seen in phlebotomy rats was earlier and significantly greater than that seen in either diet or control rats. Hemoglobin concentration returned to pre-PHZ concentrations (7.9 g/dL) in phlebotomy rats within 4 days posthemolysis. In diet rats, the maximal regenerative response (176.3 X 10(3) cells/microliter) was not seen until 8 days posthemolysis, and hemoglobin (7.5 g/dL) did not return to pre-PHZ concentrations during the 8-day study. In many aspects, the anemia seen following diet- or phlebotomy-induced iron deficiency was similar. However, the erythroid regenerative capability varied depending on the mechanism by which anemia was induced and furthermore altered the efficiency of hemoglobin production following a hemolytic event. These results suggest that the availability of iron in the diet may modulate the pathogenesis of iron deficiency anemia.
authors.affiliation: Department of Microbiology, Pathology, and Parasitology, North Carolina State University, Raleigh, NC 27606, USA. maryjo_burkhard@ncsu.edu
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Burkhard
authors.forename: Diane E.
authors.initials: DE
authors.lastname: Brown
authors.forename: John P.
authors.initials: JP
authors.lastname: McGrath
authors.forename: Vince P.
authors.initials: VP
authors.lastname: Meador
authors.forename: Douglas A.
authors.initials: DA
authors.lastname: Mayle
authors.forename: M. Joni
authors.initials: MJ
authors.lastname: Keaton
authors.forename: Wherly P.
authors.initials: WP
authors.lastname: Hoffman
authors.forename: John L.
authors.initials: JL
authors.lastname: Zimmermann
authors.forename: David L.
authors.initials: DL
authors.lastname: Abbott
authors.forename: Steven C.
authors.initials: SC
authors.lastname: Sun