Increased urinary excretion of zinc and copper by mercuric chloride injection in rats

The effects of HgCl₂ on urinary excretion of Zn, Cu and metallothionein at different time intervals were observed in male Wistar rats. The rats were given a daily intraperitoneal injection of²⁰³HgCl₂ (0.5 or 1.0 mg Hg kg^–1) for 2 days.²⁰³Hg, Zn, Cu and metallothionein in urine, kidney and liver were analyzed. Significant increases in urinary Zn and Cu concentrations were found in HgCl₂-dosed groups. Elevated urinary Zn and Cu concentrations were accompanied by an increased metallothionein excretion in urine at different time periods. Zn concentration in urine remained elevated during the entire observation period of 7 days. There were also increased concentrations of Cu and Zn in the renal cortex in one of the two exposed groups. The results indicate that urinary Cu and Zn are related to the manifestation of renal toxicity and/or the synthesis of metallothionein in kidney induced by mercury.     

Effect of dietary copper and zinc levels on tissue copper,zinc, and iron in male rats

The interaction between dietary copper and zinc as determined by tissue concentrations of trace elements was investigated in male Sprague-Dawley rats. Animals were fed diets in a factorial design with two levels of copper (0.5, 5 μg/g) and five levels of zinc (1, 4.5, 10, 100, 1000 μg/g) for 42 d. In rats fed the low copper diet, as dietary zinc concentration increased, the level of copper decreased in brain, testis, spleen, heart, liver, and intestine. There was no significant effect of dietary copper on tissue zinc levels. In the zinc-deficient groups, the level of iron was higher in most tissues than in tissues from controls (5 μg Cu, 100 μg Zn/g diet). In the copper-deficient groups, iron concentration was higher than control values only in the liver. These data show that dietary zinc affected tissue copper levels primarily when dietary copper was deficient, that dietary copper had no effect on tissue zinc, and that both zinc deficiency and copper deficiency affected tissue iron levels.     

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite. An erratum to this article is available at .     

Metabolism of heme and hemoproteins in rat liver upon administration of mercuric chloride

Rat liver delta-aminolevulinate synthase (delta-ALAS) activity in the early period after mercury chloride administration (0.7 mg per 100 g body weight) was found to be followed by free heme level increase, which was registered by the increase of heme saturation of the heme-binding protein tryptophan-2,3-dioxygenase (T-2,3-DO). delta-ALAS and heme oxygenase activity increase was observed 24 h after action. Microsomal cytochromes P450 and b5 levels decrease. Heme saturation of the T-2,3-DO returned to control level. Heme oxygenase and T-2,3-DO induction promoted hepatocytes free heme level normalization. Heme oxygenase and delta-ALAS induction role in the liver cells defense from the oxidative damage is discussed.     

Distribution of nickel,zinc, and copper in rat organs after oral administration of nickel(II) chloride

The distribution of Ni administered as NiCl₂ · 6H₂O in the drinking water (300 and 1200 ppm Ni for 90 d) was studied using male Wistar rats. Next, the effect of Ni on the concentration of zinc (Zn) and copper (Cu) in selected organs and serum was measured. The metals were analyzed in the liver, kidney, lung, spleen, brain, and serum by electrothermal (Ni) or flame (Zn, Cu) atomic absorption spectrophotometry. The results indicate that exposed rats drank less nickel solutions than the volume of water drunk by controls, but there was no mortality of animals. In comparison to control animals, a very high increase in Ni levels was found in the kidney and then lung and serum of all exposed rats. In the liver, spleen, and brain, the metal accumulation was lower. A directly proportional relation between the nickel intake and its deposition was observed in the collected organs and in the serum. The metal level did not change significantly in the course of exposure (the first analysis was after 30 d). The administration of 300 ppm Ni did not affect the zinc and copper concentration in studied organs, except the serum, where zinc content was significantly reduced. At a dose of 1200 ppm Ni, these metals were found to be depressed in the liver, kidney, serum (zinc), and copper in the kidney.     

The tissue disposition and urinary excretion of cadmium, zinc, copper and iron, following repeated parenteral administration of cadmium to rats.

The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The kidney weight relative to body weight showed a dose-related increase in weight of 25--65%. Excretion of cadmium in the urine increased directly with dosage and the increase was most significant when kidney damage had probably occurred. Administration of cadmium also resulted in dose-related increases in the urinary excretion of zinc, copper and iron. The cadmium concentration of blood increased with dosage of cadmium, and the plasma concentrations of zinc and copper were also raised but plasma iron concentration was diminished.     

Effect of mercuric chloride on various hydroxyproline fractions in rat serum

Mercuric chloride (HgCl₂) disturbs the collagen metabolism in the body which is reflected by altered hydroxyproline fractions in the serum. The aim of the present investigation was to study the effect of HgCl₂ treatment on various hydroxyproline (Hyp) fractions in rat serum and the effect of 2,3-dimercapto-1-propane sulfonic acid (DMPS) treatment on serum Hyp fractions in HgCl₂ treated rats. Other parameters studied included body weight, food intake, water intake and kidney weight. Doses of HgCl₂ used were 0.1, 0.5, 1.0, 2.0, 3.0 mg/kg body weight and that of DMPS was 100 mg DMPS/kg body weight. All the doses of HgCl₂ used caused significant (p < 0.01) alterations in free, peptide-bound and protein-bound Hyp in the serum when compared with control rats but a dose of 2 mg/kg body weight caused significant (p < 0.001) alteration even in the total serum Hyp when compared to control rats. Administration of DMPS prior HgCl₂ treatment of rats sacrificed 24 h after the treatment caused a significant decrease of 52% (p < 0.01) in free Hyp when compared to similar HgCl₂ treated rats. DMPS treatment with HgCl₂ also caused an increase of 61% (p < 0.001) and 114% (p < 0. 001) in peptide- and protein-bound Hyp respectively, when compared to HgCl₂ treated rats sacrificed 24 h after mercuric chloride and DMPS treatment. Administration of DMPS followed by HgCl₂ to rats which were sacrificed 48 h later caused no significant change in the total and free Hyp when compared to HgCl₂ treated rats which were sacrificed 48 h after the treatment. But there was a significant decrease of 40% (p < 0.001) in peptide-bound Hyp and an increase in of 77% (p < 0.001) in protein-bound Hyp when compared to HgCl₂ treated rats sacrificed 48 h after the treatment. The present study shows that HgCl₂ treatment caused significant alterations in serum Hyp fractions reflecting disturbed composition of connective tissues which were not reversed by DMPS treatment. (Mol Cell Biochem 271: 159–165, 2005)     

The longitudinal distribution of cadmium,zinc, copper,iron, and metallothionein in the small-intestinal mucosa of rats after administration of cadmium chloride

Different routes of Cd intake may influence the intestinal distribution of Cd, metallothionein (MT), and trace metals differently. Therefore, we compared the effects of parenteral and enteral administration of Cd on the distribution of trace metals and MT along the small intestine. In a first experiment three groups of rats were employed: a control, one receiving CdCl₂ within the drinking water, and another receiving sc injections of CdCl₂. In a second experiment, rats were fed three different diets with either 0, 0.3, or 1 mmol CdCl₂/kg for one and two weeks to study the time- and dose-dependent effects of orally administered Cd. Metal concentrations (Cd, Zn, Cu, Fe) were measured by atomic emission spectrometry and MT was determined by radioimmunoassay. Intestinal MT levels did not show proximodistal gradients in controls or after sc administration of Cd, but orally administered Cd increased mucosal MT levels longitudinally from the duodenum to the ileum. Cd levels paralleled those of MT. Compared with the metal concentrations in the controls, sc administration of Cd did not change intestinal Zn, Cu, and Fe levels. Oral administration of Cd, however, increased Cu and decreased Fe levels in the intestinal mucosa significantly. The second experiment revealed that only high dietary concentrations of Cd increase intestinal Cd and MT levels longitudinally toward the distal parts, whereas at lower dietary concentration the longitudinal distribution was reversed. This shows that different routes and doses of Cd intake lead to a different trace metal and MT distribution and emphasizes the role of dietary Cd in the local induction of small-intestinal MT.     

Effect of dietary chitosans on trace iron, copper and zinc in mice

Dietary chitosans with different molecular weight M_w and the degree of deacetylation DDA (high molecular weight chitosan HCS with M_w 7.60 × 10⁵ and DDA 85.5%, middle molecular weight chitosan MCS with M_w 3.27 × 10⁴ and DDA 85.2%, chito-oligomer COS with M_w 0.99 × 10³ and DDA 85.7% and water-soluble chitosan WSC with M_w 3.91 × 10⁴ and DDA 52.6%) were used at the 1.05% level to feed mice for 90 days. Afterwards no pathological symptoms, clinical signs or deaths were observed. The body weight of mice in chitosan group and control group showed no significant difference. Although HCS, COS and WSC had no significant effect on the level of Fe, Zn and Cu in the tested mice’s liver, spleen, heart and kidney, MCS significantly increased the level of Fe, Zn and Cu in liver. Therefore dietary ingestion of chitosan did not depress the level of Fe, Zn and Cu in mice.     

Inhibition of iron and copper uptake by iron, copper and zinc

Interactions of micronutrients can affect absorption and bioavailability of other nutrients by a number of mechanisms. In aqueous solutions, and at higher uptake levels, competition between elements with similar chemical characteristics and uptake process can take place. The consequences of these interactions may depend on the relative concentrations of the nutrients. In this work, we measure the effects of increasing concentrations of iron, zinc, and copper on iron and copper uptake in Caco-2 cells. Intracellular Fe or Cu levels were affected by incubating with increased concentrations of metals. However, when the cells already had different intracellular metal concentration, the uptake of Fe or Cu was nor affected. In competition studies, we showed that Cu and Zn inhibited Fe uptake, and while Fe inhibited Cu uptake, Zn did not. When the three metals were given together (1:1:1 ratio), Fe or Cu uptake was inhibited approximately 40%. These results point to a potential risk in the absorption and bioavailability of these minerals by the presence of other minerals in the diet. This aspect must be considered in food supplementation and fortification programs.     

Influence of dietary carbohydrate on copper, iron, and zinc status of the rat.

Rats were fed diets containing starch, sucrose, glucose, or fructose as the carbohydrate source, and the influence of these carbohydrates on copper, iron, and zinc status was determined. It was found that copper absorption was reduced in animals receiving glucose. This reduction was exaggerated when a high level of iron was present in the diet, indicating a possible antagonism between iron and copper at the site of absorption. Iron and zinc status of the animals also appeared to be influenced to some extent by dietary carbohydrate.     

Metabolism of zinc and copper in the neonate: Effect of cadmium administration during late gestation in the rat on the zinc and copper metabolism of the newborn

Rats that have been treated with Cd (1.0 mg/kg body wt., i.v.) on the 18th day of gestation give birth to young, the livers of which are low in Zn, but not in Cu. With increasing age after birth the hepatic concentrations of total and thionein-bound Zn in these animals increase rapidly to maxima at about 7 days, approx. 6 days later than in the newborn of normal dams, whereas the liver Cu concentration reaches a higher maximum at an earlier age than in the control neonate. This rapid uptake of Cu into the liver of the newborn of the Cd-treated dam is not accompanied by a concomitant increase in the concentration of soluble thionein-bound Cu.Cadmium-treatment of the dam retards the weight gain of the liver and, at least during the first 6–8 days postpartum, the increase in body wt. of the newborn. When the hepatic concentrations of thionein-bound Zn is expressed relative to liver wt. instead of age, there is no significant difference between the newborn from normal and Cd-treated dams.The Zn concentrations in blood, brain, stomach, duodenum, pancreas, spleen, kidney and muscle of newborn rats either remain constant, or increase only slightly with age after birth and are not affected significantly by the administration of Cd to the dam in late gestation. This treatment, which probably increases the demand for Zn in the newborn, delays the deposition of Zn in bone and causes a reduction in the Zn concentration of the skin. The Cu concentrations in skin and bone, as well as in other organs of the newborn during the first 24 days postpartum, seem to be unaffected by Cd-treatment of the dam.It is suggested that hepatic Zn-thionein has an essential function in the Zn metabolism of the liver, but is unlikely to control the supply of Zn to other organs in the newborn rat.     

Effect of phosphorus and zinc on the growth and phosphorus,zinc, copper,iron and manganese nutrition of rice

Summary A greenhouse experiment was conducted to study the effect of phosphorus and zinc application, in three lowland alluvial rice soils (Haplustalf) on the growth of rice and the concentration of phosphorus, zinc, copper, iron and manganese in shoots and roots. The results showed that application of phosphorus and zinc significantly increased the dry matter yield of shoots, grains and roots. Application of phosphorus caused a decrease in the concentration of zinc, copper, iron and manganese both in shoots and roots. Application of zinc also similarly lowered the concentration of phosphorus, copper and iron, but increased that of manganese in shoots and roots. The decrease in the concentration of the elements in the shoots was not due to dilution effect or to the reduced rate of translocation of the elements from the roots to tops. This has been attributed more to the changes in the availability of the elements in soil resulting from the application of phosphorus and zinc.     

Effect of aldosterone on the serum zinc, copper, and magnesium concentrations in the rat

Possible regulation of trace metal metabolism by various steroid hormones has been reported by a number of investigators. The purpose of the present study was to determine the effect of aldosterone on the serum copper, zinc, and magnesium concentrations in the rat. Male and female rats were infused with aldosterone for up to 72 h and the serum copper, zinc, and magnesium concentrations were determined. The serum zinc concentration exhibited a transient decrease with a nadir at 24 h. No significant change was observed in serum magnesium or copper that was directly attributable to aldosterone. The mechanism by which aldosterone affects the transient serum zinc decrease was not demonstrated, but several possibilities were discussed.     

Effect of nickel(II) chloride on iron content in rat organs after oral administration

The effect of oral administration of nickel(II) chloride on iron content in serum and certain body organs of rats was investigated. The male adult rats were given 300 and 1200 ppm Ni in drinking water for 90 d. The iron content in serum, liver, kidney, lung, spleen, and brain was analyzed 30 and 90 d postexposure. The hemoglobin, hematocrit, and body and organ weights were also measured. Nickel given in drinking water led to a pronounced increase in iron content in serum and the liver, as compared to control rats. This effect was related to Ni concentration in the water. There was not great time-dependent difference in the iron content as a response to continuous nickel treatment, except the lung of 1200-ppm Ni-treated rats. In relation to hematological parameters, Ni supplementation did not affect any of them. Body weight significantly decreased, and lung weight was significantly increased in 1200-ppm Ni-treated rats. The results of this study indicate that nickel ingestion (300 and 1200 ppm in the drinking water) induces the iron uptake by serum and some organs of rats. The highest amount of iron was found in the liver of all exposed animals, and the time-dependent difference in iron content was observed in the lung of 1200-ppm Ni-treated rats.     

Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos

Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism.     

Effect of zinc supplementation on the antioxidant,copper, and iron status of physically active adolescents

Puberty associated with intense physical activity results in oxidation stress. Zinc supplementation may benefit antioxidant capacity although it may also affect iron and copper status. This study evaluated the effect of zinc supplementation on antioxidant, zinc and copper status of physically active male football players (13 years ± 0.4 years), divided in two groups and studied during 12 weeks: Zn‐supplemented (Zn‐SUP, 22 mg Zn d^?1 as zinc gluconate, n = 21) and placebo (PLA, n = 26). At baseline, there was no significant difference in biochemical indices between the two groups. After treatment, plasma zinc and erythrocyte iron increased in both groups (p < 0.001); urinary zinc increased (p < 0.001) only in Zn‐SUP, and erythrocyte zinc decreased (p = 0.002) only in PLA. Plasma iron and copper decreased (p = 0.01 and p = 0.015, respectively) only in Zn‐SUP. Plasma ferric‐reducing ability and plasma conjugated dienes increased, and erythrocyte osmotic fragility decrease in both groups, although the latter two were significantly lower in Zn‐SUP compared to PLA (p < 0.01). In conclusion, our study indicates that the use of 22 mg d^?1 of supplemental zinc during 12 week in adolescent athletes did not affect growth, improved markers of antioxidant status but reduced plasma iron and copper. Therefore, it appears that the use of zinc supplementation by healthy adolescent athletes benefits their antioxidant capacity but impairs copper and iron nutritional status. Copyright © 2009 John Wiley & Sons, Ltd.