Effects of Changes in Dietary Zinc, Copper and Selenium Supply and of Endotoxin Administration on Metallothionein I Concentrations in Blood Cells and Urine in the Rat

Abstract

These studies were designed to investigate the effects of low dietary zinc, copper or selenium intake of certain types of stress and of injection of zinc, copper or cadmium on metallothionein I (MT-I) concentrations in the blood and urine of rats. The aim was to establish whether such measurements could be of value in the diagnosis of zinc deficiency. Marginal zinc deficiency rapidly caused a major decrease in MT-I levels in the blood cells and to a lesser extent in urine. Injection of zinc and also of cadmium and copper had the opposite effect and increased MT-I concentrations in both samples, although the effects of zinc on blood cells and urine were relatively transient. The MT-I in the blood cells was associated mainly with the erythrocytes. No changes in blood or urine MT-I levels were found in copper- and selenium-deficient rats. Neither cold stress nor restriction of food intake for 24 h had any significant effect on MT-I levels in the blood cells or urine. Endotoxin injection increased urinary MT-I excretion in both zinc-adequate and zinc-deficient rats but did not affect blood cell MT-I levels in either group of animals. It appears therefore that assay of erythrocyte MT levels could be of particular value in the diagnosis of zinc deficiency, especially when it is accompanied by stress or infection.

Absence of metallothionein-3 produces changes on MT-1/2 regulation in basal conditions and alters hypothalamic-pituitary–adrenal (HPA) axis

“…It is generally accepted that the expression of MT-1/2 is highly inducible in response to several conditions like stress and inflammation (Chua et al, 2012;Chung et al, 2008;Bremner et al, 1987;Sato and Bremner, 1993;Ghoshal et al, 1998) Glucocorticoids appear to have a role in brain MT regulation, at least in basal conditions as previously noted (Hidalgo et al, 1994a). In our laboratory, we have shown in earlier experiments that glucocorticoids appear to mediate brain MT-1 induction in some but not all brain areas indicating that other factors must be involved.…”

Erythrocyte metallothionein as an index of zinc status in humans.

“…Furthermore, RIA' data indicate that plasma and erythrocyte metallothionein 1 concentrations were reduced to very low levels within days in rats fed a zinc-deficient diet (6). In addition, although endotoxin produces a large increase in the plasma metallothionein concentration, bone marrow and erythrocyte metallothionein 1 are increased only slightly (<2-fold) (7). Therefore, erythrocyte metallothionein appears much less responsive to stress and infection than either plasma metallothionein or plasma zinc in experimental animals and may be a more stable indicator of zinc status in humans.…”

“…Furthermore, rat erythrocyte metallothionein also appears to be rapidly removed from the circulation-with its decrease in concentration correlated with decrease in dietary zinc intake (6). Binding of plasma metallothionein to the erythrocyte apparently does not account for the presence of this protein in these cells (7). Therefore, as the erythrocyte ages, metallothionein appears to be degraded rather than retained within the cell and lost with the older cells when they are removed from the circulation.…”

Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

“…In rats and Syrian hamsters, endotoxin treatment increases Zn and decreases Cu concentrations in liver and decreases Zn and increases Cu concentrations in plasma (6,7). At the cellular level, endotoxin treatment increases the amount of Zn bound to MT, a cytosolic transition metal-binding protein, in the liver (8) and in cultured hepatocytes (9) and increases the urinary excretion of MT (10). Induction of MT synthesis protects macrophages against endotoxin-induced cell killing (I 1).…”