Cadmium In Liver Research Articles

Subcellular distribution of heavy metals in liver and kidney of a narwhal whale ( Monodon monoceros): An evaluation for the presence of metallothionein

1. The subcellular distribution of Zn, Cd, Cu and Hg in liver and kidney from a narwhal was determined by ultracentrifugation and gel filtration. 2. Most of the total mercury in the liver and kidney was bound by the cellular pellet (88 and 73%, respectively). Of the total mercury, 7 and 11% was in the form of methylmercury in the liver and kidney, respectively. 3. More than half (74%) of the total Zn and Cu in the kidney was in the cytosol and somewhat less than this was in the cytosol of the liver. 4. Almost all of the cadmium in liver and kidney (88 and 92%, respectively) was in the cytosol. 5. Cytosolic fractions from liver and kidney were evaluated for the presence of metallothionein by analysing for Zn, Cd, Hg, Cu, Fe and —SH groups, by molecular weight estimation and by u.v. absorption spectra. Metallothionein was found in these organs in estimated concentrations similar to those present in terrestrial and other marine mammals.

Cadmium in wheat grain: its nature and fate after ingestion.

Cadmium intake in humans derives primarily from vegetable foods, yet the extent to which the chemical form and dose of cadmium in such foods influences the fate and toxicity of this metal is poorly understood. We have compared the fate in mice of trace levels--approximating that in agriculturally produced grain--and high levels of cadmium supplied as wheat grain with that of cadmium supplied as CdCl2. The amounts and forms of the metal in kidney and liver, target organs in cadmium accumulation, were compared. Results indicate that, in mice, cadmium orally administered as grain and that as CdCl2 have a similar fate in terms of organ distribution and the nature of the Cd-forms in kidney and liver. A low dose of either form resulted in higher kidney versus liver cadmium. Preliminary characterization studies indicate that cadmium in wheat grain occurs primarily as an 11,000-dalton, aqueous-soluble complex, which is not inducible by cadmium.

Heavy metal concentrations in tissues of Virginia river otters.

Concentrations of lead, cadmium, zinc and copper in liver, kidney and bone samples of otter harvested during the 1979-1980 and 1980-1981 trapping seasons were determined by atomic absorption spectrophotometry. Correlations between metal concentrations and age for all three tissues were nonsignificant. Correlations among the concentrations of the four elements in liver and kidney samples were also nonsignificant for otter samples in both years. The highest correlation coefficient (0.47) was found between zinc and copper concentrations in liver samples from otters trapped during the 1979-1980 trapping season. (JMT)

Effects of dietary cadmium on mallard ducklings

Mallard ( Anas platyrhynchos) ducklings were fed cadmium in the diet at 0, 5, 10, or 20 ppm from 1 day of age until 12 weeks of age. At 4-week intervals six males and six females from each dietary group were randomly selected, bled by jugular venipuncture, and necropsied. Significant decreases in packed cell volume (PCV) and hemoglobin (Hb) concentration and a significant increase in serum glutamic pyruvic transaminase (GPT) were found at 8 weeks of age in ducklings fed 20 ppm cadmium. Mild to severe kidney lesions were evident in ducklings fed 20 ppm cadmium for 12 weeks. No other blood chemistry measurement, hematological parameter, or tissue histopathological measurement indicated a reaction to cadmium ingestion. Body weight, liver weight, and the ratio of the femur weight to length were not affected by dietary cadmium. Femur cadmium concentration in all ducklings 12 weeks of age declined from the values detected at 4 and 8 weeks of age. Liver cadmium concentrations were significantly higher in relation to the increased dietary levels and in relation to the length of time the ducklings were fed the cadmium diets. At 12 weeks of age the cadmium concentration in liver tissue was twice that in the diet.

In vivo screening of potential antidotes for chronic cadmium intoxication.

Nineteen chelating agents have been screened under identical conditions of metal loading in an attempt to establish their relative ability to mobilize cadmium from the liver and kidney in mice with chronic cadmium intoxication. The compounds investigated were divided into five groups: polyaminocarboxylic acids, monothiols, dithiols, macrocycles, and a miscellaneous category. Only 2,3-dimercaptopropanol (BAL) and sodium diethyldithiocarbamate (NaDDTC) were able to produce a statistically significant (at the 95% level) reduction in the cadmium content of the kidney. The closely related dithiols sodium 2,3-dimercaptopropane-1-sulfonate and 2,3-dimercaptosuccinic acid produced statistically significant increases in the liver cadmium contents, as did N-(2-mercaptopropionyl)-glycine. The reduction in kidney cadmium levels produced by both BAL and NaDDTC was just under 40%.

Metabolism of parenterally administered zinc and cadmium in livers of newborn rats

The interaction of injected zinc and cadmium with metallothionein was investigated in newborn rats. Tissues of 5-day-old rats were removed 24 h after a single injection (Sc) of saline or zinc (20 mg/kg, body wt.) or cadmium (1 mg/kg, body wt.) with 2.5 μCi of 65Zn or 109Cd or 5 μCi of [ 35S]cysteine. Injection of zinc resulted in a 75% increase in the hepatic zinc concentration with a concomitant elevation of metallothionein ( P < 0.001), zinc in metallothionein increased by 45% ( P < 0.05); [ 35S]cysteine incorporation indicated the induced synthesis of metallothionein. Injection of cadmium did not alter either metallothionein or zinc levels in liver, but cadmium in cytosol was preferentially bound to metallothionein. Neither treatment altered hepatic copper metabolism and copper in metallothionein, nor renal zinc and metallothionein levels. These data indicate that zinc injection can elevate hepatic zinc levels and induce metallothionein synthesis in newborn rats despite high basal levels; cadmium injection does not induce metallothionein synthesis, though cadmium is avidly sequestered by pre-existing metallothionein. The differences in the induction of metallothionein by these divalent cations can be explained by the differences in their binding affinities for thiol groups in intracellular metallothionein.

Liver cadmium concentrations in metal industry workers.

In vivo neutron activation analysis of liver cadmium concentration was performed in 285 metal workers, 130 of whom had been exposed to cadmium in the workplace. Only two workers showed pathological levels in excess of 50 ppm. However, mean liver, urine and blood cadmium levels were significantly different as between the exposed and the unexposed workers. In vivo neutron activation analysis of liver cadmium concentration is easy to perform and can readily be used for industrial screening whenever a hazard is suspected.

Variation of cadmium accumulation among Japanese.

Human liver, renal cortex, and heart muscle from 394 autopsied Japanese who had lived in eight districts of Japan were sampled. Subjects included 200 males between 0 to 89 yr of age and 194 females between 0 to 94 yr of age. Cadmium, copper, and zinc in both liver and renal cortex, as well as cadmium in heart muscle were compared by district, sex, age, and smoking habits. Statistical results revealed that the difference of each heavy metal distribution by eight districts is significant and that cadmium and zinc levels in liver and renal cortex sampled from north-central Japan were the highest. This probably results from the larger intake of dietary cadmium and zinc via rice since this area is known as one of the better rice growing regions in Japan. Although there is a lack of precise information on smoking habit, cadmium in liver and zinc in liver and renal cortex of males smoking eight or more cigarettes per day were statistically higher than that of nonsmokers and those who smoked less than seven cigarettes per day. However, cadmium in renal cortex was not significant between the two smoking groups. Further studies should be performed to determine the health significance of an increased intake of cadmium by populations from the viewpoint of global biogeochemistry.

Extent of cadmium accumulation and its effect on essential metals in liver, kidney, and body fluids.

Cadmium was injected sc into female Wistar rats at a dose of 3.0 mg Cd/kg body weight, 4 times a week for 1, 2, 3, 4, 5, and 6 wk. Cadmium and five essential metals in the livers and kidneys were determined simultaneously by inductively coupled plasma-atomic emission spectrometry. Concentration of cadmium in the livers increased linearly up to 3 wk, remained at an almost constant and highest value (440 micrograms Cd/g wet liver) for the following 2 wk, and then decreased. The difference between cadmium in the whole livers and cadmium bound to heat-stable proteins was wider during the plateau than during the other periods. Cadmium in the kidneys was close to a plateau after 6 wk of injections. Concentrations of zinc in the livers and copper in the kidneys changed dramatically with injections of cadmium, and the changes were related to the changes in concentrations of the two metals in plasma and urine. Concentration of iron in the kidneys decreased with injections of cadmium. The content ratio of calcium to magnesium was high in the case of liver edema and was suggested to be an indicator. Cadmium in urine was assumed to originate from the liver in the case of high accumulation of the metal.

The critical level of cadmium in human renal cortex: A reevaluation

The previously published estimate (160 ppm) of the critical level of renal cortical cadmium (Cd) (Roels et al., Environ. Res., 26 (1981) 217–240) has been reassessed after the depth of the left kidney was measured in each worker by echography. The correction introduced for kidney depth demonstrates that the critical liver cadmium level of 30 ppm corresponds to a corrected critical level of cadmium in renal cortex of 216 ppm. This critical cadmium level in renal cortex (CdKc) protects probably more than 90% of male workers from developing Cd-induced renal dysfunction.

Trace metals in the common porpoise, Phocoena phocoena

Mercury, cadmium, copper and zinc concentrations in brain, liver, kidney, heart and spleen of twenty-six specimens of the common porpoise ( Phocoena phocoena) are presented. Mercury and cadmium levels in liver and kidneys tended to increase with length of animal, but copper and zinc levels show no such trends. The proportion of methylmercury to total mercury (9%–57%) in the liver decreased with increasing total mercury concentrations. Lead, chromium, nickel and cobalt levels were below the analytical detection limits (0·5, 1·0, 1·0 and 2·5 μg −1, respectively).

Influence of dietary zinc or cadmium on hair and tissue mineral concentrations in rats and goats.

Three experiments were conducted to determine whether concentrations of minerals in hair and other tissues of rats and goats are affected by level of dietary Zn or Cd. In the first experiment, rats were fed diets that contained 10.3, 20.5, 33.7, 41.3 or 52.9 micrograms Zn/g for 57 d. Rats fed the diet that contained 10.3 micrograms Zn/g suffered from mild Zn deficiency, as indicated by depressed feed intakes and slower growth rates than rats fed diets containing higher amounts of Zn. Zinc concentrations in hair (P less than .01), liver (P less than .01) and kidney (P less than .01) increased as dietary Zn increased. Confidence intervals for dietary Zn concentration predicted from Zn analysis of hair were large. In the second experiment, rats were fed diets that contained .1, 4.0, 7.6, 10.1 or 15.9 micrograms Cd/g for 57 d. Total growth, feed intake, feed efficiency and liver, kidney and testes weights were not affected (P greater than .05) by dietary Cd concentration. Cadmium increased linearly in liver (P less than .01) and kidney (P less than .01) and quadratically in testes (P less than .01) as Cd intake increased, but Cd in hair was not affected by dietary level of Cd. High correlations between Cd concentrations in liver (R2 = .88) and kidney (R2 = .90) and dietary Cd concentration indicate that Cd intakes of rats may be accurately predicted from Cd analyses of these tissues. In the third experiment, goats were fed diets containing 0, 10.4, 18.0 or 28.5 micrograms Cd/g for 125 d. Growth, feed intake, feed efficiency and liver and kidney weights were not affected by dietary Cd intake. Cadmium in hair samples was not affected by level of dietary Cd; however, cadmium in liver (P less than .01), kidney (P less than .01) and proximal duodenum (P less than .01) increased as dietary Cd increased. Cadmium in liver, kidney, lungs and proximal duodenum was highly correlated (R2 = .67, .89, .57, .49, respectively) with dietary Cd concentration.

Toxicologic studies in growing sheep fed silage corn cultured on municipal sludge-amended acid subsoil.

Field corn was grown on subsoil, pH 5.5, that had been amended with 100 dry tons per acre (224 metric tons per hectare) of municipal sewage sludge from Syracuse, New York. The corn plants containing 3.88 ppm dry weight of cadmium were field-chopped and ensiled, and the silage was fed to growing sheep for 225 d. The sheep fed the sludge-grown corn silage showed a significantly (10 higher feed efficiency, (2) higher hepatic microsomal p-nitroanisole O-demethylase activity, and (3) higher concentrations of cadmium in liver and kidney and nickel in kidney as compared to the control animals. No significant treatment effects were observed in mutagenic responses for animal feed or feces samples. No consistent treatment effects were noted during histopathologic examination of sheep tissues.

Effect of partial hepatectomy on hepatic metallothionein and glutathione levels and cadmium distribution in different tissues

The changes in hepatic metallothionein (MT) and glutathione levels and cadmium distribution were investigated 72 hr after a subcutaneous administration of 1.5 mg Cd 2+ kg as CdCl 2H 2O to normal and partially hepatectomized rats. Partial hepatectomy had no effect on native metallothionein content. Cadmium and MT content in livers of partially hepatectomized rats were comparatively lower than in those of intact rats. However, cadmium content significantly increased in other organs of partially hepatectomized rats. Cadmium exposure decreased glutathione level only in intact rats. The effects of partial hepatectomy and regeneration on hepatic MT level and metal distribution are discussed.

Some Metabolic Interrelationships Between Toxic Levels of Cadmium and Nontoxic Levels of Selenium Fed to Rats

Male rats were fed vitamin E-adequate, Torula yeast-based diets for 30 days to assess the influence of dietary selenium (0, 0.1, or 1.0 ppm) on the toxicity of dietary cadmium (0, 30, or 60 ppm). At all selenium levels, increased cadmium intake depressed feed consumption, reduced feed efficiency and lowered body weight gain. In liver, concentrations of cadmium and zinc increased, and iron concentration decreased with increased intake of cadmium. Dietary selenium did not affect concentrations of cadmium, zinc, iron or copper in liver. Blood hemoglobin level declined and relative heart weight (g/100 g body wt) increased with increased intake of cadmium. Increased selenium intake partially alleviated the cadmium-induced depression in blood hemoglobin levels in rats fed diets that contained 30 ppm cadmium, and partially ameliorated the cadmium-induced increase in heart size in rats fed either 30 or 60 ppm cadmium. Hepatic and renal glutathione peroxidase (GSH-Px) activity increased with increased selenium intake. Increased cadmium intake did not affect renal GSH-Px activity. Hepatic GSH-Px activity in rats fed diets that contained 0.1 ppm selenium decreased with increased cadmium intake; however, hepatic GSH-Px activity was not affected by dietary cadmium in rats fed diets that contained 1.0 ppm selenium. Interactions between nontoxic levels of dietary selenium and relatively high levels of dietary cadmium apparently resulted in an antagonism of selenium metabolism by cadmium in some systems, and partial amelioration of cadmium toxicity by selenium in other systems.cadmium-selenium interaction cadmium toxicity glutathione peroxidase

Metabolism of cadmium in the neonate: Effect of hepatic zinc, copper and metallothionein concentrations on the uptake of cadmium in the rat liver

The accumulation and subcellular distribution of Cd 2+ (1 mg/kg body wt, i.p.) in the liver of the neonatal rat is age-dependent. At 4 hr after treatment the liver Cd 2+ contents in the 12-day-old, 20-day-old and adult rat are similar and greater than in the 2-day-old animal. The differences in hepatic Cd 2+ concentration in the older age groups are consistent with the nonlinear weight gain of the liver in the developing animal. In the hepatic cytosol Cd 2+ is incorporated into a high molecular weight and metallothionein fractions and transferred from the former to the latter. This process occurs less rapidly with increasing age. The uptake of Cd 2+ by the whole liver and the hepatic metallothionein is not related to the total liver concentration of Zn 2+ or copper and is not significantly influenced by the concentration of pre-existing metallothionein or the concentration of thionein-bound Zn 2+ or copper. The results are discussed in relation to the possible effects of Cd 2+ on the liver metabolism and tissue distribution of Zn 2+ and copper in the developing animal.

Additive Statistical Effects of Cadmium and Lead on Heart Related Disease in a North Carolina Autopsy Series

The association of heart-related mortality with tissue cadmium and lead in a study of autopsies performed on persons who resided in a soft-water, leached-soil area of North Carolina was examined. Liver cadmium concentrations and aortic lead level were indices of these elements. Both cadmium and lead levels had statistically significant correlations with cause of death (heart-related disease vs. non-heart-related disease, excluding cancer). Although cause of death was significantly associated with age, the association with cadmium and lead persisted after statistical adjustment for the effect of age. The combined effects of cadmium and lead provided sufficient information in an additive model to predict cause of death correctly for 80% of the cases, with age contributing insignificantly. These findings indicate the intimate relation of these two trace metals with increased risk of heart-related mortality, even in light of known conventional causes of such deaths.

Measurement of cadmium in liver and kidney using in vivo techniques.

Measurement of cadmium in liver and kidney using in vivo techniques.

The concentration and retention of cadmium in liver and kidney tissues of rats

Abstract A total of 72 male Sprague‐Dawley rats were assigned to three groups using a 3 X 3 factorial design. Animals were injected IP every three days for 29 days with 0, 1.0 or 2.5 mg CdCl2/kg of body weight. Total cumulative CdCl2 doses were 0. 9.0 or 22.5 mg/kg of body weight. Animals were sacrificed on day 1, 7 or 21 following injections. Liver and kidney tissues were collected and analyzed for Cd concentrations. The Cd‐treated groups exhibited significant increases in Cd concentrations in both tissues. An average of 0.85, 19.86 and 48.44 μg/g of wet liver tissue and a mean of 0.78, 11.53 and 31.14 μg/g of wet kidney tissue for the 0, 1.0 and 2.5 mg CdCl2/kg of body weight groups, respectively, were observed. The amount of Cd in these tissues remained significantly high over the 21‐day observation period.

Direct determination of cadmium in the NBS bovine liver by Zeeman atomic absorption spectrometry using the graphite miniature-cup

黒鉛ミニチュアカップを用いるゼーマン原子吸光分析法によるNBS bovine liver 中のカドミウムの直接定量に関する検討を行った.カドミウムは揮発性の高い元素であるため加熱プログラム開始直前に硫酸5μlを添加することを試みた.その結果,検量線の直線性及び測定精度は著しく向上した.硫酸濃度は4N,炭化は240℃で120秒間が最適であった.試料量とカドミウム吸光度の直線関係は,試料量(0.05～0.50)mgの範囲で成立した.感度(吸光度0.0044を示す値)は,カドミウム3×10-12gであった.標準添加法によるNBS bovine liver 中のカドミウムの定量値は,0.25μg g-1でNBSの保証値(0.27±0.04)μg g-1と良く一致した.精度は変動係数として9.6%であった.