title: Long-term intake of a high zinc diet causes iron deficiency anemia accompanied by reticulocytosis and extra-medullary erythropoiesis.
abstract: To elucidate the pathophysiology of zinc (Zn)-induced iron (Fe) deficiency anemia (IDA), we examined hemoglobin (Hb) concentrations, hematocrit (Ht) levels, numbers of circulating red blood cells (RBC) and reticulocytes, values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), serum Zn, Fe and erythropoietin (EPO) concentrations and histopathological changes in the bone marrow, spleen and liver using rats fed with a standard or high Zn diet for 20 weeks. Rats fed with the high Zn diet exhibited a significant decrease in Hb concentrations, Ht levels and MCV, MCH and MCHC values, indicating microcytic hypochromic anemia characterized by Fe deficiency. Also, a marked decrease in serum Fe concentrations was seen in rats fed with the high Zn diet relative to rats fed with the standard diet. Interestingly, the number of RBC was comparable in both groups of rats, although a decrease in the number of RBC is ordinarily seen in IDA. There were reticulocytosis and extra-medullary erythropoiesis in the spleen and an increase in serum EPO concentrations in rats fed with the high Zn diet vs. those on the standard diet. These observations suggest that both reticulocytosis and extra-medullary erythropoiesis in the spleen played a role in maintaining the number of RBC in rats fed with the high Zn diet, preventing further progression of anemia. Further, increased production of EPO may be involved in the induction of reticulocytosis and extra-medullary erythropoiesis in the spleen.
authors: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan. hryanagisawa@jikei.ac.jp
authors: Hiroyuki
authors: H
authors: Yanagisawa
authors: Yuichi
authors: Y
authors: Miyakoshi
authors: Koh
authors: K
authors: Kobayashi
authors: Kensaku
authors: K
authors: Sakae
authors: Ichiro
authors: I
authors: Kawasaki
authors: Yuji
authors: Y
authors: Suzuki
authors: Jun'ichi
authors: J
authors: Tamura
mesh_terms: D000747:Anemia, Hypochromic / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004032:Diet; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D004920:Erythropoiesis / Q000187:drug effects*; D006400:Hematocrit; D007501:Iron / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017701:Reticulocyte Count; D045262:Reticulocytosis / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D015032:Zinc / Q000097:blood / Q000633:toxicity*
chemical_list: D007501:Iron; D015032:Zinc