metallothionein and Anemia--Hypochromic

The concentrations of essential metal ions in various compartments of the human body are accurately regulated (homeostasis). Irregularities in the accumulation or depletion of the trace elements may lead to well characterized diseases. This review covers the metabolism of zinc regulations by which the intracellular and extracellular levels are kept in physiological range, biological functions, as well as pathological states that develop in its altered metabolism. The focus is on the molecular mechanisms of zinc ion traffic between compartments of the body and cells and their sequestration, gene regulations that regulate the ion fluxes via biological membranes and their storage, zinc-mediated cell and tissue damages, and development of symptoms in zinc deficiency is also discussed.

Topics: Anemia, Hypochromic; Dietary Supplements; Homeostasis; Humans; Intestinal Absorption; Metallothionein; Signal Transduction; Trace Elements; Zinc

Topics: Adult; Age Factors; Aged; Anemia, Hypochromic; Animals; Cadmium; Cadmium Poisoning; Calcium; Copper; Diet; Female; Humans; Iron; Male; Metalloproteins; Metallothionein; Middle Aged; Pregnancy; Selenium; Zinc

The effects of iron deficiency and of restriction of food intake on blood and tissue metallothionein-I (MT-I) concentrations in rats were investigated. Compared to ad libitum fed controls, MT-I concentrations in the blood cells of the iron-deficient rats were higher, whereas concentrations in pair-fed control rats were lower. Iron deficiency also increased MT-I concentrations in the bone marrow but concentrations in the liver were unchanged and those in the kidneys were reduced. The MT-I in the blood cells was associated mainly with the lighter cell fractions which were rich in reticulocytes. It is suggested that concentrations of MT-I in blood cells reflect erythropoietic activity.

Topics: Anemia, Hypochromic; Animals; Blood Cells; Body Weight; Bone Marrow; Diet; Eating; Iron; Kidney; Liver; Male; Metallothionein; Rats

Effects of cadmium (Cd) on in vitro and in vivo erythropoiesis in rats were studied by methylcellulose colony assay. Cd suppressed the in vitro growth of late erythroid progenitors (CFU-E) in a dose-dependent fashion and did not lose its inhibitory potency with increasing doses of erythropoietin (EPO). In addition, in marrow suspension cultures, Cd did not significantly influence 59Fe incorporation into both the cells and heme, and the Cd dose-responsive inhibition curve of the number of living cells was similar to that of CFU-E. These results suggest that the suppression of CFU-E colony formation by Cd is not due to the blocking of either EPO action to stimulate the growth of CFU-E or the iron incorporation into the cells ahd heme, but due to its direct cytotoxic effect. The colony suppression by Cd could be prevented by adding metallothionein to the cultures. On the other hand, oral administration of Cd to animals (100 mg/liter in drinking water) induced an iron deficiency anemia characterized by microcytic hypochromic red cells, decreased plasma iron, and increased total iron binding capacity. Marrow CFU-E density steadily increased as plasma iron decreased due to Cd administration and reached a plateau after 50 days. Plasma EPO titers were also found to be elevated in such a Cd-induced anemia. Parenteral iron administration during the Cd drinking period could completely prevent the development of iron deficiency anemia and the increase of both CFU-E and plasma EPO. There was a hyperbolic correlation between CFU-E and plasma iron or transferrin saturation. These results demonstrate that oral CD administration produces bone marrow hyperplasia at the CFU-E level due to iron deficiency.

Topics: Anemia, Hypochromic; Animals; Cadmium; Cell Survival; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Hematopoietic Stem Cells; Iron; Iron Deficiencies; Male; Metallothionein; Rats; Rats, Inbred Strains