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.     

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.     

Influence of dietary cadmium on the distribution of the essential metals copper,zinc and iron in tissues of the rat

The effect of long-term dietary cadmium treatment upon the distribution of the metals copper, iron and zinc has been compared in various organs of male and female rats. The renal accumulation of cadmium was similar in both sexes without a plateau being reached. In contrast, the hepatic accumulation of cadmium was higher in the female than in the male rat and a plateau was observed after 30–35 weeks of dietary cadmium treatment. Most of the cadmium which accumulated in these organs was recovered in the metallothionein fraction and the concentration of hepatic cadmiumthionein in the female rat was correspondingly higher than in the male rat. Accumulation of cadmium was associated with an increased zinc concentration in the liver and an increased copper concentration in the kidney; these increases were correlated with increases in liver and kidney metallothioneins induced by cadmium. Uptake of cadmium into organs other than liver and kidney occurred to a small extent but was not associated with changes in the concentration of copper and zinc. Cadmium also accumulated in the intestinal mucosa where it could be recovered in a fraction corresponding to metallothionein. A loss of iron from the liver and kidney was also observed following dietary cadmium treatment and involved mainly a loss of iron from ferritin.     

The effects of age and sex on seven elements of Sprague-Dawley rat organs

This study reports age-related changes in 7 element (iron, copper, zinc, manganese, mercury, cadmium and lead) concentrations in the liver, kidney and brain of male and female Sprague-Dawley rats from 1 to 364 days of age. Atomic absorption spectrometry was used for the measurements. Copper, mercury and cadmium in the male and female kidneys increased from weaning until 127 days of age, as did iron concentrations in the female liver and kidney. After 127 days, especially, the copper concentration in the female kidney and cadmium concentration in the male and female kidney increased further. Consistent and statistically significant (P less than 0.05) sex differences in element concentrations were found for three elements (iron, copper and zinc). Except for the zinc concentration in the liver from 50 to 72 days, iron (in liver and kidney), zinc (in kidney) and copper (in liver, kidney and brain) concentrations in female rats during the adult stage, were all higher than those of male rats. Isolated differences for other elements (manganese, mercury and cadmium) were also found. The data will be helpful when setting up long-term animal investigations of the biological effect of elements.     

Comparative distributions of zinc, cadmium and mercury in the tissues of experimental mice

Different groups of mice were injected with cadmium, zinc and mercury. Zinc injections had no effect on zinc tissue levels while both mercury and cadmium accumulated in various tissues. Cadmium persisted in the tissues much longer than mercury, and while the mercury concentrations began to decline as soon as dosing ceased, cadmium concentrations in kidney and intestine increased even after dosing ceased. There appeared to be an interrelationship between cadmium concentrations in spleen and intestine which warrants some further investigations. There was a linear, but discontinuous, effect of cadmium on zinc concentrations in liver, kidney and pancreas which may depend on metallothionein biochemistry. Mercury injections had no effect on zinc metabolism. It is proposed that differences in the rate of excretion of cadmium and mercury from the kidney could explain the differential accumulation of cadmium and mercury in animals.     

Effect of dietary calcium on cadmium absorption and retention in suckling rats

The effect of calcium supplementation on absorption and retention of cadmium in the suckling period was evaluated in Wistar rat pups of both sexes. Animals were maintained in the litters with the mother rats and supplemented with 1%, 3% or 6% calcium (as CaHPO₄×2H₂O) in cow's milk by artificial feeding from day of birth 6 through 14. All rats were exposed to cadmium (as CdCl₂×H₂O) either orally or parenterally. Oral cadmium dose of 0.5 mg/kg body weight a day was administered through nine-day period of calcium supplementation and parenteral cadmium dose was injected subcutaneously in a single dose of 0.5 mg Cd/kg body weight prior to calcium supplementation. On experimental day 10 (at the age of pups of 15 days) all animals were killed and the liver, kidneys, brain and carcass (body without organs and skin) were removed for element analyses. Cadmium and essential elements calcium, zinc and iron were analysed in the tissues by atomic absorption spectrometry. Results showed that after oral exposure cadmium concentrations in all calcium-supplemented groups were significantly decreased in the organs and carcass and that the effect was dose-related. No such effect of calcium was found after parenteral cadmium exposure. Calcium supplementation per se significantly increased calcium concentration in the carcass and had no effect on iron in organs and zinc in carcass. It was concluded that calcium supplementation during the suckling period could be an efficient way of reducing oral cadmium absorption and retention without affecting tissue essential trace element concentrations.     

A comparison of the accumulation and protein binding of environmental cadmium in the gills, kidney and liver of rainbow trout (Salmo gairdneri Richardson)

Rainbow trout were exposed to cadmium in their aquarium water for different lengths of time and at different concentrations. More than 99% of the total body loads accumulated under all such conditions of exposure was found in the liver, kidney and gills. Comparison of the metal-binding proteins in these organs indicated that two low mol. wt proteins sequestered the cadmium while zinc was bound to metallothionein. Cadmium was not found in association with metallothionein unless artificially high concentrations were introduced either by intraperitoneal injection of the fish or by dialysis of tissue extracts in vitro.     

Zinc,cadmium, mercury and selenium in polar bears (Ursus maritimus) from Central East Greenland

Muscle, liver, and kidney tissues from 38 polar bears (Ursus maritimus) caught in the Scoresby Sound area, Central East Greenland, were analysed for zinc, cadmium, mercury and selenium. In general, cadmium concentrations were low in muscle, liver and kidney tissue, with geometric means (g.m.) of 0.022 (range: <0.015–0.085), 0.841 (range: 0.092–3.29) and 13.1 (range: 1.04–115) g Cd/g wet weight (ww) respectively. This finding can be explained by low cadmium levels in the blubber of ringed seals. The concentration of mercury in muscle tissue was low (g.m. 0.071; range: 0.039–0.193 g Hg/g ww), whereas concentrations in liver and kidney tissue were relatively high (liver: g.m. 7.87; range: 1.35–24.8 g Hg/g ww, and kidney: g.m. 15.2; range: 1.59–66.6 g Hg/g ww). Mercury and cadmium were positively correlated with age in liver and kidney. Zinc was positively correlated with age in kidney, and selenium was correlated with age in liver. Contrary to other marine mammals, polar bears had higher mercury levels in the kidneys than in the liver. In all three tissues polar bears had significantly lower cadmium levels than ringed seals from the same area. Mercury levels were likewise significantly lower in the muscle tissue of polar bears than in ringed seals, whereas levels in the liver and kidney were significantly higher. The previous geographic trend for cadmium and mercury found in Canadian polar bears could be extended to cover East Greenland as well. Hence cadmium levels were higher in Greenland than in Canada, while the opposite was the case for mercury. Greenland polar bears had higher mercury and cadmium contents in livers and kidneys than polar bears from Svalbard. The mercury levels in muscle and liver tissue from polar bears from East Greenland were twice as high as found in bears from western Alaska, but half the levels found in northern Alaska. Cadmium and zinc were partially correlated in kidney tissue, and this was found for mercury and selenium as well. Cadmium and zinc showed molar ratios close to unity with the highest concentrations occurring in kidney tissue, while the levels of zinc exceeded cadmium in muscle and liver tissue by up to several decades. Mercury and selenium showed molar ratios close to unity in liver and kidneys.     

Biological function of metallothionein. VI. Metabolic interaction of cadmium and zinc in rats

The accumulation and depletion of cadmium in liver and kidney metallothionein (MT) and the effects of dietary zinc deficiency on cadmium metabolism were studied in rats. The accumulation of cadmium in liver MT started to plateau after 80 days, but there was a linear accumulation of this element in kidney MT over the entire 300-day experiment. Cadmium in MT fractions was depleted very slowly when rats were changed to a diet without cadmium. The accumulation of cadmium in MT also caused zinc to accumulate in this protein, even in rats fed zinc-deficient diets. However, the reverse situation was found not to be true; zinc did not cause cadmium to accumulate in MT. Dietary zinc deficiency limited the binding of injected¹⁰⁹Cd to MT of liver, but not of kidneys or testes. However, zinc-deficient rats fed cadmium in their diets metabolized cadmium similarly to zinc-supplemented rats, suggesting that zinc deficiency does not limit the ability of cadmium to stimulate MT synthesis.     

Low ambient temperature decreases cadmium accumulation in the liver and kidneys of the bank vole (Clethrionomys glareolus)

The importance of photoperiod and ambient temperature on the accumulation of cadmium in the liver and kidneys of bank voles was determined in the present study. Males and females, aged 1 month, were given 3.0 g Cd ml^–1 drinking water and divided into four groups according to photoperiod (16 h light/8 h dark and 8 h light/16 h dark) and ambient temperature (20 or 5°C); liver and kidneys were removed for cadmium as well as copper, iron and zinc analyses at the end of 6 weeks. Bank voles exposed to 5°C in both photoperiods consumed approximately 30% less water containing cadmium than those kept at 20°C. However, the total accumulation of cadmium in the liver and kidneys of males and females exposed to the low temperatures was 4.3–4.8 and 2.2–3.3 times less than that in animals maintained at room temperature in the long and short photoperiod, respectively. Simultaneously, the low temperature brought about an increase in the copper concentrations in the liver (12–43%) and kidneys (47–78%), giving rise to an inverse correlation between the cadmium accumulation and the tissue copper concentration. In contrast to cadmium and copper, the concentrations of iron and zinc were affected primarily by photoperiod. These findings indicate that ambient temperature is an important determinant of cadmium retention in the bank vole. It appears that low temperature decreases tissue cadmium accumulation not only by reducing cadmium intake but also through changes in copper metabolism.     

Trace Elements Status in Selenium-Deficient Rats—Interaction with Cadmium

Although the metabolic and toxicological interactions between essential element selenium (Se) and toxic element cadmium (Cd) have been reported for a long time, the experimental studies explored mostly acute, high-dose interactions. Limited data are available regarding the effects of Se-deficiency on toxicokinetics of cadmium, as well as on the levels of key trace elements—copper, zinc, and iron. In the present study, male and female Wistar weanling rats (n = 40/41) were fed either Se-deficient or Se-adequate diet (<0.06 or 0.14 mg Se per kilogram diet, respectively) for 12 weeks, and from week 9 were drinking water containing 0 or 50 mg Cd/l as cadmium chloride. At the end of the 12-week period, trace element concentrations were estimated by AAS. Selenium-deficient rats of both genders showed significantly lower accumulation of cadmium in the liver, compared to Se-adequate rats. Zinc and iron hepatic levels were not affected by Se-deficiency. However, a significant elevation of copper was found in the liver of Se-deficient rats of both genders. Cadmium supplementation increased zinc and decreased iron hepatic level, regardless of Se status and decreased copper concentration in Se-adequate rats. Se-deficiency was also found to influence the effectiveness of cadmium mobilization in male rats.     

Inhibition of rat liver and kidney arginase by cadmium ion

Cadmium ion activates arginase from many species of organisms but is an inhibitor of arginase from many other species. The purpose of this study was to investigate the inhibition of rat liver and kidney arginase by cadmium ion. Rat kidney arginase was inhibited by much lower concentrations of cadmium ion than rat liver arginase. Cadmium ion was a mixed noncompetitive inhibitor of both rat liver and kidney arginase. Cadmium ion enhanced the substrate activation of rat kidney arginase while still inhibiting the enzyme. Cadmium ion prevented the substrate inhibition of rat kidney arginase by fluoride while still inhibiting the enzyme. Cadmium ion also inhibited rat kidney arginase in the presence of manganese ion.     

Inhibition of rat liver and kidney arginase by cadmium ion

Cadmium ion activates arginase from many species of organisms but is an inhibitor of arginase from many other species. The purpose of this study was to investigate the inhibition of rat liver and kidney arginase by cadmium ion. Rat kidney arginase was inhibited by much lower concentrations of cadmium ion than rat liver arginase. Cadmium ion was a mixed noncompetitive inhibitor of both rat liver and kidney arginase. Cadmium ion enhanced the substrate activation of rat kidney arginase while still inhibiting the enzyme. Cadmium ion prevented the substrate inhibition of rat kidney arginase by fluoride while still inhibiting the enzyme. Cadmium ion also inhibited rat kidney arginase in the presence of manganese ion.     

Cadmium and zinc content of fish from an industrially contaminated lake

Eleven species of fish from an industrially-contaminated lake were analysed for whole body cadmium and zinc content by atomic absorption spectrophotometry. Cadmium and zinc content of fish were species related, and most species accumulated these trace metals to levels significantly higher than background. Maximum concentrations detected were 13.60 μg Cd g⁻¹ (dry wt) in a bluegill and 820 μg Zn g⁻¹ in a redear sunfish. Cadmium content was much more variable than zinc content. Distributions of concentrations of both cadmium and zinc in fish were lognormal, and concentrations of both metals tended to decrease in higher trophic levels. Zinc concentrations significantly decreased as total length increased in three species.     

Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading

The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants.     

In vivo neutron activation analysis of organ cadmium burdens

In vivo neutron activation measurements of liver and kidney cadmium have been mae in 77 exposed workers and 101 referents. Cadmium levels were higher in exposed workers than in referents; both in liver, 25.7 cf. 0.6 μg/g, and kidney, 17.9 cf. 2.7 mg. The 19 referents who never smoked had lower mean organ cadmium burdens than the other referents, the difference achieving statistical significance in the kidney,p<.01. Cigaret smoking was estimated to increase cadmium body burden by 370-140 μg/pack year. These referent cadmium levels are similar to, although slightly below, previous in vivo and autopsy data.

     

The long-term effect of cadmium exposure through food on the postnatal development of the bank vole (Clethrionomys glareolus Schreber, 1780)

Cadmium is well known for its toxicity to the animal body. However, its effect on pregnancy and the development of young animals is still not well understood. This study examined such effects, using bank voles captured from the wild to make the results closer to those which could be expected in the natural environment. One group of animals was fed 7 microg g(-1) cadmium in the food, a second 35 microg g(-1), and a third no cadmium, as a control. The concentrations of cadmium in the whole bodies of young bank voles were determined on the 3rd, 5th, or 10th day of life. The cadmium level in the bodies of animals exposed to 35 microg g(-1) of cadmium was significantly higher than in those from either the control group or the group receiving 7 microg g(-1) of cadmium, which did not differ from each other. The cadmium level did not change with animal age in any of the study groups. Concentrations of Zn, Cu, and Fe were also determined in the whole body of young animals, as cadmium is known to disturb the metabolism of these essential metals through antagonistic activity. Both Cu and Fe levels were negatively correlated with cadmium concentrations, while a positive correlation was found between zinc and cadmium in the young animal bodies. Also found was higher offspring mortality in the group receiving 35 microg g(-1) of cadmium in food. There was no difference in young animal body weight between the study groups.     

Uptake of six heavy metals by oat as influenced by soil type and additions of cadmium,lead, zinc and copper

Summary The influence of heavy metal additions on availability and uptake of cadmium, lead, zinc, copper, manganese and iron by oat was studied. The experiments were carried out as pot experiments using sandy loam, sandy soil and organic soil. Selective extractants were used to remove metals held in different soil fractions.Lead and copper were preferently bound by organics and oxides, zinc by oxides and inorganics, and cadmium by inorganics and organics.Addition of cadmium to the soils resulted in higher cadmium concentrations in all plant parts but lower concentrations of lead, zinc, copper, manganese and iron, and the accumulation indexes of these metals were also lower when cadmium was added to the soil.Addition of cadmium plus lead, zinc and copper resulted in higher cadmium concentrations in leaves and straw of plants grown in sandy loam and sandy soil, but lower concentrations when plants were grown in organic soil as compared with the results when cadmium was added separately. The transfer of cadmium, lead, zinc and copper from soil to plant was greatest from sandy soil, and zinc and cadmium were more mobile in the plant than were lead and copper.Cadmium concentrations in leaves correlated significantly with CaCl₂ and CH₃COOH extractions in sandy loam and sandy soil and with CH₃COOH extractions in organic soil.Generally, the total metal uptake was lowest from organic soil.     

Levels of toxic and essential elements in arctic fox in Svalbard

Concentrations of cadmium, mercury, lead, arsenic, selenium, copper, zinc, manganese and iron in liver, and cadmium in kidneys, were analysed in 95 carcasses of arctic fox (Alopex lagopus) caught in Svalbard during three winter seasons from 1984 through 1986. The hepatic concentration ranges of cadmium, mercury, lead and arsenic were 0.1–2.4, 0.01–2.2, < 0.5–2.9 and 0.01–1.3 g·g^–1 WW, respectively. The range of cadmium concentration in the kidneys was from 0.2 to 13 g·g^–1 WW. Cadmium and mercury concentrations were higher in adult animals than in juveniles. The average concentrations of cadmium and lead were similar to recently published levels in polar bear from Svalbard, but the mercury concentrations were lower. Significant geographical differences were observed between trapping areas. Foxes caught north of Isfjorden had lower levels of liver iron and higher levels of all other elements analysed than those caught south of Isfjorden. The recorded concentrations of heavy metals indicate a moderate degree of exposure, which most likely is of natural origin.Gunnar Norheim died January 9, 1991     

The effect of heavy metal accumulation on metallothionein content in selected tissues of bank voles and yellow-necked mice caught near a steelworks and zinc smelter

The effect of cadmium, zinc, and copper accumulation on metallothionein content in the selected tissues of bank voles and yellow-necked mice trapped near the Sendzimir Steelworks in Krakow and the zinc smelter in Bukowno were analysed. The Borecka Forest was chosen as a control area. The highest cadmium concentration, 32.98 microg g(-1) dry weight, was detected in the kidneys of the bank voles caught in the Bukowno area. Zinc and copper concentrations in the tissues did not exceed the critical values. Metallothionein content in the liver and kidneys was associated with heavy metal accumulation in the tissues. The highest content of sulphydryl groups was detected in the livers of the bank voles trapped within the neighbourhood of the zinc smelter in Bukowno. The highest level of disulphide bonds was found in the kidneys of the bank voles from the same area.