Interaction between zinc and iron in rats

The importance of interactive effects, of minerals in general, on nutrient requirements is becoming increasingly recognized. The interaction between iron and zinc has not been as widely investigated. The metabolic interrelationships between dietary iron and zinc have been known for years, but some subtle relationships may have gone unrecognized. Because nutrient interactions are not necessarily linear in nature, it may be inadequate to apply linear statistical models to study the interaction between zinc and iron. In this study, we used traditional as well as a nonlinear approach in analyzing experimental results from groups of rats fed a wide range of dietary zinc and iron. Male weanling Sprague-Dawley rats were used in a 5 × 4 factorially arranged experiment. Dietary variables were iron (as ferric citrate) at 4, 12, 24, 48, or 96 μg Fe/g diet and zinc (as zinc carbonate) at 5, 10, 20, or 40 μg Zn/g diet. After 7 wk, hematological parameters were measured and plasma ceruloplasmin and cholesterol were determined. In addition to interactive effects as shown by analysis of variance, the application of log-linear analysis to the experimental data revealed a far broader range of interactions between dietary iron and zinc. As a result of our experiment and its quantitative analysis, we conclude that the interaction between iron and zinc is nutritionally important and that dietary iron affected the response of many blood parameters to dietary zinc. The complete dataset can be found at http://www.gfhnrc.ars.usda.gov/fezn. U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.     

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl₂) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.     

The influence of dietary iron on zinc in rat

The purpose of this study was to clarify the influence of iron on zinc status. The animals were divided into four groups, consisting of five rats in each group. The control group was fed on basal diet with adequate levels of zinc and iron, whereas the experimental group was fed diets containing different levels of iron ad libitum for 15 d. Low levels of iron (LFe) significantly increased the zinc absorption percentage but there was a decrease in high (HFe) and very high iron (VHFe) level groups (p<0.001). The retention percentage changes were found to be parallel to the changes in the absorption percentage curve. It was found that zinc (per total dry tissue) and Zn-65 (per total tissue) increased in the rats fed the LFe, whereas in general they decreased in the rats fed the HFe and VHFe diets. Significant changes were found in the duodenum and liver. Zn-65 (per g wet tissue) significantly increased in the brain and liver in the LFe group, but there was a decrease in the duodenum, ileum, kidney, liver, and brain in the HFe and VHFe groups. Changes in the level of zinc (per g dried tissue) were found to be parallel to the changes in Zn-65 in all the groups. The dietary proportions of iron appear to influence zinc metabolism at the intestinal and cellular transport levels over a given period of time.     

The effect of various dietary zinc concentrations on the biological interactions of zinc,copper, and iron in rats

Three groups (14 rats each) were fed one of the following diets for 8 wks: a control purified basal diet containing 12 ppm zinc, 5 ppm copper, and 35 ppm iron; the basal diet with less than 2 ppm zinc; or the basal diet supplemented with 1000 ppm zinc. Rats fed the zinc-deficient diet had decreased weight gain, moderate polydipsia, and intermittent mild diarrhea. The zinc-supplemented rats had a cyclical pattern of food intake and weight loss from weeks 5 to 8. Tissue concentrations suggest that zinc and copper were not mutually antagonistic with chronic dietary imbalances. If tissue element concentrations reflected intestinal uptake, then competition and/or inhibition of intestinal uptake occurred between zinc and iron. The fluctuations in tissue element concentrations that occurred with increased duration of the study were at variance with previous studies of shorter time periods. The dietary proportions of zinc, copper, and iron appear to influence zinc, copper, and iron metabolism at the intestinal and cellular transport levels over a given period of time.     

Essential trace elements selenium, zinc, copper, and iron concentrations and their related acute-phase proteins in patients with vivax malaria

The aim of the present study is to evaluate the status of plasma essential trace elements selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) concentrations and their related acute-phase proteins, ceruloplasmin (Cp), ferritin, transferrin (Tf), and albumin levels in patients with vivax malaria. Plasma Cu and Zn concentrations were determined by atomic absorption spectrometry (AAS). Se concentrations were determined by graphite furnace AAS. Fe, Cp, Tf, and albumin levels were determined by colorimetric methods. Plasma Se, Fe, and albumin levels were found to be significantly lower (p<0.01, p<0.001, and p<0.05, respectively) and Cu, Cp, and ferritin levels and Cu/Zn ratios were significantly higher (p<0.001, p<0.001, p<0.001, and p<0.05, respectively) in patients when compared with those of healthy subjects. Plasma, Tf, and Zn levels were not found to be significantly different (p>0.05) in patients and controls. There were positive important correlations between Cu and Cp (r=0.908, p<0.001), Zn and albumin (r=0.633, p<0.001), and negative correlations between Fe and ferritin content (r=−0.521, p<0.05) and Fe and Tf (r=−0.616, p<0.01) in the patients group. Our findings demonstrated that plasma essential trace elements Se, Cu, and Fe change, but these changes might be dependent on acute-phase proteins, which were regulated as a part of defense strategies of the organism, induced by hormonelike substances.     

Effect of dietary nickel and iron on the trace element content of rat liver

The level and/or form of dietary iron, dietary nickel, and the interaction between them affected the trace element content of rat liver. Livers were from the offspring of dams fed diets containing 10–16 ng, or 20 μg, of nickel/g. Dietary iron was supplied as ferric chloride (30 μg/g) or ferric sulfate (30 μg, or 60 μg). In nickel-deprived rats fed 60 μg of iron/g of diet as ferric sulfate, at age 35 days, levels of iron and zinc were depressed in liver and the level of copper was elevated. At age 55 days, iron was still depressed, copper was still elevated, but zinc also was elevated. In rats fed 30 μg of iron/g of diet as ferric chloride, liver iron content was higher in nickel-deprived than in nickel-supplemented rats at 30, but not at 50, days of age. Also manganese and zinc were lower in nickel-deprived than in nickel-supplemented rats at age 35 days if their dams had been on experiment for an extended period of time (i.e., since age 21 days). Thus, the levels of copper, iron, manganese, and zinc in liver were affected by nickel deprivation, but the direction and extent of the affects depended upon the iron status of the rat.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

Effect of nicotinic acid on zinc and iron metabolism

Nicotinic acid has functional groups capable of forming complexes with trace metals. The present study examines the effect of nicotinic acid supplementation on absorption and utilization of zinc and iron. In vitro zinc uptake by human erythrocytes was studied using blood samples of 10 healthy subjects. It was found that 8 moles nicotinic acid or NADP increased ⁶⁵Zn uptake by 38.9% and 43.1% in fasting, and by 70.9% and 28.1% in postprandial conditions. In animal experiments, nicotinic acid supplementation to finger millet based diet resulted in significant enhancement of percent zinc absorption, liver zinc and growth of weanling mice (P < 0.05). When mice were fed with nicotinic acid-deficient, -adequate and -excess synthetic diets for four weeks it was observed that, in comparison with the nicotinic acid-deficient diet, percent zinc absorption, intestinal zinc, percent haeomoglobin and liver iron increased significantly under nicotinic acid-adequate and -excess conditions. The results obtained suggested that nicotinic acid, in addition to its known effect on growth and metabolism, may be playing an important role in enhancing zinc and iron utilization.     

Change in apparent and true absorption and retention of dietary zinc with age in rats

Two groups of 16 rats each were fed the same diet with 12.9 ppm Zn. Nine days after each animal was injected with⁶⁵Zn for assessing fecal zinc of endogenous origin, zinc intake and excretion were determined for a six-day period at the age of about five (group I) and nine (II) weeks. At mean growth rates of 5.1 and 5.2 g/day, food consumption per gram of gain was 2.01 g in group I vs 2.86 g in II. Overall, zinc retention amounted to 21 vs 25 μg Zn/g of gain. Apparent absorption averaged 92 vs 74% of Zn intake (132 vs 189 μg/day), while true absorption averaged 98 vs 92%. It was concluded that endogenous fecal zinc excretion was limited to the indispensable loss (F _em) in group I (7 μg/day), while it exceeded this minimum loss in group II (33 μg/day). True retention, which reflected total zinc utilization (true absorption times metabolic efficiency), was derived from apparent absorption plusF _em (11 μg/day for group II according to the greater metabolic body size of the rats). It averaged 98% of Zn intake in group I vs 80% in group II. The mean metabolic efficiency was 100% vs 87%. The conclusion was that these marked differences between age groups in utilizing the dietary zinc reflected the efficient homeostatic adjustments in absorption and endogenous excretion of zinc to the respective zinc supply status.     

Variation in the distribution of trace elements in hepatoma

There are many reports of reduction of zinc level and rise of copper level in serum of patients with liver disease. However, there are a few reports that compare the trace elements in tumor tissues and nontumor tissues of the liver with hepatoma. We studied trace element distribution in tumor tissues and nontumor tissues of liver with hepatoma and compared them with data from normal liver tissues. Zinc (Zn), copper (Cu), selenium (Se), cadmium (Cd), mercury (Hg), and iron (Fe) were chosen as the trace elements to be observed. We observed falls of Zn, Cd, and Hg levels in tumor tissues and the rise of Cu level as a result of this investigation. Zn, Cd, and Hg levels in tumor tissues were significantly lower than those in nontumor tissues and Zn, Cd, and Hg levels in nontumor tissues were significantly lower than in normal liver tissues. This tendency was clearer for Cd and Hg than for Zn. Although the distribution of Cu was not significant, a distribution contrary to that of Zn was shown. These findings indicate that the distribution of Zn, Cd, and Hg can serve as supportive evidence that could be useful as a tumor marker. Selenium showed almost the same accumulation tendency among tumor tissues, nontumor tissues, and normal livers. Although correlation was observed among most metals in the normal liver, there was almost no correlation in tumor tissues.     

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl₄)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.     

Influence of cadmium on the distribution of the essential trace elements zinc and copper in the liver and kidneys of rats

Cd induced changes of Zn and Cd distribution in the liver and kidneys were studied in relation to Cd metallothionein (MT) synthesis. Wistar male rats were given CdCl₂ by sc injection of .8, 1.5, and 3.0 mg Cd/kg three times a week for three weeks. Cd levels of liver and kidneys increased with the increment of Cd dosage and 80–90% of Cd was found in the cytosol. The MT fractions contained 80–89% cytosolic Cd in the liver and 55–75% Cd in the kidneys. Zn concentrations in the liver increased following Cd administration, But Zn in the kidneys showed only slight increase. There was a distinct decrease of Cu concentration in the liver of the 3.0 mg group. In contrast, Cu concentrations in the kidneys increased about three times in the .8 and 1.5 mg Cd groups, but Cu in the 3.0 mg group showed only 1.5 times increase. The changes of these metal concentrations were observed mainly in the cytosol. Non-MT-Cd in the kidneys was maximum in the 1.5 mg group, but the 3.0 mg group showed significant decrease. In parallel with this decrease of Cd, Cu and Zn in the kidneys showed similar decrease. When the kidneys are injured, Zn and Cu appear to leak from this organ.     

Changes in iron, calcium, magnesium, copper, and zinc levels in different tissues of riboflavin-deficient rats

To clarify the changes of mineral levels in different tissues of riboflavin-deficient rats, Wistar rats were separated into three groups. One group was fed a diet ad libitum that was deficient in riboflavin. The other two were fed either the complete diet that was weight-matched to the riboflavin-deficient group or fed a complete diet ad libitum. In riboflavin-deficient rats, the hemoglobin concentration and riboflavin contents of blood, liver, and kidney were significantly decreased, compared with weight-matched and ad libitum-fed controls. The mineral concentrations of tissues are summarized as follows: The iron (Fe) concentration in the heart, liver, and spleen was decreased in the riboflavin-deficient group compared with the other groups. Calcium (Ca) and magnesium (Mg) concentrations in tibia were decreased in the riboflavin-deficient group compared with the other two groups. Copper (Cu) concentration was increased in the heart and liver when the riboflavin-deficient group was compared with the other groups. Zinc (Zn) concentration was increased in tibia when the riboflavin-deficient group was compared with the other groups.     

Serum and tissue trace elements in patients with breast cancer in Taiwan

The objective of this study was to compare levels of four elements (zinc, copper, selenium, and iron) in the serum and tissue of 68 breast tumor patients (benign and malignant), from a teaching hospital in central Taiwan. Samples of normal tissue (5 cm away from tumor) were also taken from patients with malignant tumors. Only serum was taken from the 25 healthy persons in the control group. Results showed that Zn, Cu, Se, Fe, Cu/Zn, Cu/Se, and Cu/Fe were present in different amounts in the serum of each of the three groups. Zn and Se levels were lower in the serum of the two tumor groups compared to the control group. In tissue samples, Zn, Cu, Se, and Fe concentrations were different in each of the three groups. The malignant tissue had the highest levels of all four elements. In advanced-stage malignant tumors, levels of Cu and the ratios of Cu/Fe and Cu/Zn (in both serum and tissue) were highest. The ratios of serum Cu/Zn, Cu/Fe, and Cu/Se were also higher in malignant patients. The cutoff value of serum Cu/Zn was 1.2 (sensitivity and specificity were both 100%). The Cu/Zn ratio was highest in the advanced stages of cancer and was a better diagnostic tool for breast cancer than Cu/Se and Cu/Fe. The authors suggest that change of trace elements in serum and tissue might be useful and significant as biomarkers involving the initial plastic process.     

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 .     

Sequential thoracentesis: minor change of zinc compared to other selected essential trace elements in the serum

This study first indicates that the serum trace element Zn tends to decrease in the course of sequential thoracenteses. Other selected essential elements such as copper (Cu), manganese (Mn), molybdenum (Mo), and cobalt (Co) do not reveal loss changes in their serum levels. Therefore, Zn should be monitored in patients who undergo repeated thoracentesis. To measure the magnitude of changes in serum trace elements and the clinical relevance of potential imbalances, concentrations of the essential elements are analyzed in 57 serum/effusion pairs obtained from 5 patients (4 male, 1 female; age 28–78 yr) who underwent repeated thoracenteses as a result of recurrent pleural effusion. All patients declined other therapeutic options such as chemical pleurodesis and /or chest tube placement. The total volumes of fluid removed ranged from 2.3 to 19.3 L and the frequency of thoracentesis ranged from 6 to 15 within a period of 102–174 days. Two patients had benign pleural disease and three had malignancies. Three patients suffered from pleural effusions resulting from exudates (total protein content >3.0 g/dL, LDH >200 U/L), and two resulting from transudates (total protein <3.0 g/dL, LDH <200 U/L). All trace elements were simultaneously determined by inductively coupled argon plasma-mass spectrometry. In addition, the concentrations of the following clinically relevant parameters were analyzed by standard methods: total protein, pH, leukocyte count, lactate dehydrogenase, and glucose.     

Concentrations of cadmium,zinc, copper,iron, and metallothionein in liver and kidney of nonhuman primates

To evaluate the species specificity of Cd accumulation and the relationship of Cd with other essential metals and metallothionein (MT), the concentrations of Cd, Zn, Cu, and Fe in the liver and kidney and the MT concentrations in the soluble fractions of the liver and kidney were determined in Cd-uncontaminated nonhuman primates (11 species, 26 individuals) kept in a zoo and two wild-caught Japanese macaques. The compositions of metal-binding proteins in the soluble fractions were also investigated by high-performance liquid chromatography (HPLC). The hepatic Cd concentration was 0.03–14.0 μg/g and the renal Cd concentration was 0.35–99.0 μg/g, both varying greatly and being higher in nonhuman primates, which were more closely related to man. The hepatic Zn concentration was 24.0–176 μg/g and the renal Zn concentration was 13.5–138 μg/g, showing 7- to 10-fold differences, and a correlation (r=0.558, p<0.01) was found between renal Zn and renal Cd concentrations. It was proved that in the liver, MT is more closely correlated with Zn (r=0.795, p<0.001) than with Cd (r=0.492, p<0.01) and that in the kidney MT is correlated with both Cd (r=0.784, p<0.001) and Zn (r=0.742, p<0.001). HPLC analysis of metals bound to MT-like protein in chimpanzees, de Brazza’s monkeys, and Bolivian squirrel monkeys showed that more than 90% of Cd in both the liver and kidney, approx 40% of Zn in liver and 28–69% of Zn in kidney were bound to MT-like protein. The higher percentage Zn was bound to high-molecular protein.     

Serum and hair levels of zinc and other elements in dogs with visceral leishmaniasis

The aim of this study was to determine the zinc, iron, copper, calcium, phosphorus, and magnesium levels in blood serum and zinc and copper levels in hair of dogs with canine visceral leishmaniasis. The serum zinc and iron levels were found to be significantly lower in diseased dogs than those of healthy controls. Serum copper levels were significantly higher, whereas no significant differences were observed for calcium, phosphorus, and magnesium. There were no significant differences in the zinc and copper levels in hair. Our results show that the serum zinc, iron, and copper levels are altered in canine leishmaniasis.     

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.