Copper Concentrations In Kidney Research Articles

P0735ELAVATED INTRACELLULAR COPPER CONTRIBUTES A UNIQUE ROLE TO KIDNEY FIBROSIS BY LYSYL OXIDASE MEDIATED MATRIX CROSSLINGKING

Abstract Background and Aims Copper is an essential trace element required for many biological processes. Some studies have demonstrated that copper accumulating was related to liver fibrosis and lung fibrosis, but the underlying mechanism is not very clear. Copper is the essential unit of lysyl oxidase (LOXs), which are the key enzymes of crosslinking of extracellular matrix. Method Sprague-Dawley rats were divided into the sham group, unilateral ureteral obstruction (UUO) operated group and UUO treated with copper chelating agents tetrathiomolybdate (TM). Rat kidney fibroblast cells (NRK-49F) were used in vitro. The concentration of copper, the LOXs activity and the degree of cross-linking of extracellular collagen were detected in vivo and vitro. Results (1) The copper concentration in serum, urine and kidney of rats increased significantly at 7 days after UUO surgery; After treatment of TGF-β1, the intracellular copper concentration was increased significantly in cells; The concentration of copper in patients` serum is on the rise with the progression of chronic kidney disease (CKD). (2) The expression of CTR1 was upregulated in the kidneys of UUO rats; The level of CTR1 was increased significantly by TGF-β1 in vitro; (3) Blockage of Smad2/3 suppresses TGF-β1-induced expression of CTR1; (4) Downregulation of CTR1 significantly inhibited the intracellular copper concentration; (5) The activity of LOXs was increased significantly after TGF-β1 treatment; (6) Downregulation of CTR1 significantly inhibited the activity of LOXs and the cross-linking of extracellular collagen induced by TGF-β1 in vitro; (7) The concentration of copper, the degree of collagen cross-linking and the deposition of collagen were decreased in the kidney tissue of UUO rats after treatment with TM. The concentration of intracellular copper, the activity of LOXs and the degree of collagen cross-linking were attenuated with treatment of TM in vitro. Conclusion We firstly found that the intracellular copper accumulating was closely to renal fibrosis. The underlying mechanism was related with the increasing expression of CTR1 and activity of LOXs. Treatment with TM ameliorated the renal fibrosis. This study presented a novel treatment target for renal fibrosis.

Alterations in Copper Homeostasis in Rabbit Model of Atherosclerosis

Copper concentrations decrease in atherosclerotic tissues. The present study was undertaken to determine overall alterations in copper homeostasis in the pathogenesis of atherosclerosis. New Zealand white rabbits, aged 10‐weeks‐old, were fed a rodent chow diet containing 1% (w/w) cholesterol or the same diet without cholesterol as control. Twelve weeks after respective diet feeding, the animals were euthanatized by sodium pentobarbital. Rabbits fed cholesterol‐containing diet developed hyperlipemic as defined by a significant increase in the total plasma cholesterol and atherosclerotic lesions in aorta. Copper concentrations in the atherosclerotic tissues were significantly decreased while serum copper concentrations were increased in the hyperlipemic animals in comparison with controls. A detailed analysis revealed that copper concentration in abdominal aorta of the hyperlipemic rabbits was negatively correlated with the severity of the atherosclerotic lesion, stenosis of the lumen area, and collagen deposition. In addition, copper concentrations in the kidney of hyperlipemic rabbits were increased, but in the heart, liver, spleen and lung were decreased. These results suggest that in the pathogenesis of atherosclerosis, changes in copper homeostasis are not only observable in the atherosclerotic tissues, but also in multiple organ systems. These changes would be additive to atherosclerosis as a high risk of cardiovascular disease in humans.Support or Funding InformationWest China Hospital, Sichuan University(A) The percentage of the aortae staining positively for lipid(Longitudinal of suprarenal abdominal aortae was stained with oil red O). Sections of infrarenal abdominal aortae were stained with EVG for microscopic quantification of lesion areas, (B) the atherosclerotic lesion area and (C) the percent of stenosis of lumen area. Collagen fibers in the lesions were assessed by picrosirius red staining, the percent of Collagen in lesion area. (*P < 0.05)Figure 1The concentration of copper in tissues and plasma.(A) cardiac copper concentration; (B) liver copper concentration; (C) spleen copper concentration; (D) lung copper concentration; (E) kidney copper concentration; (F) duodenum copper concentration; (G) abdominal aortic copper; (H) plasma copper concentration. (*P < 0.05)Figure 2

Trace metals from historical mining sites and past metallurgical activity remain bioavailable to wildlife today

Throughout history, ancient human societies exploited mineral resources all over the world, even in areas that are now protected and considered to be relatively pristine. Here, we show that past mining still has an impact on wildlife in some French protected areas. We measured cadmium, copper, lead, and zinc concentrations in topsoils and wood mouse kidneys from sites located in the Cévennes and the Morvan. The maximum levels of metals in these topsoils are one or two orders of magnitude greater than their commonly reported mean values in European topsoils. The transfer to biota was effective, as the lead concentration (and to a lesser extent, cadmium) in wood mouse kidneys increased with soil concentration, unlike copper and zinc, providing direct evidence that lead emitted in the environment several centuries ago is still bioavailable to free-ranging mammals. The negative correlation between kidney lead concentration and animal body condition suggests that historical mining activity may continue to play a role in the complex relationships between trace metal pollution and body indices. Ancient mining sites could therefore be used to assess the long-term fate of trace metals in soils and the subsequent risks to human health and the environment.

Arsenic, cadmium, cobalt, copper, lead, mercury, molybdenum, selenium and zinc concentrations in liver, kidney and muscle in Australian sheep

Matched muscle, liver and kidney samples from 152 sheep in different states of Australia were analysed for trace elements. Mean levels found in muscle, livers and kidneys were 0.010, 0.010 and 0.011mgkg−1 (fresh weight) for arsenic; 0.0035, 0.280 and 0.853mgkg−1 for cadmium; 0.006, 0.060 and 0.044mgkg−1 for cobalt; 0.74, 66.0 and 2.72mgkg−1 for copper; 0.007, 0.040 and 0.057mgkg−1 for lead; 0.0025, 0.0034 and 0.0061mgkg−1 for mercury; 0.014, 1.05 and 0.44mgkg−1 for molybdenum; 0.09, 0.31 and 0.95mgkg−1 for selenium; and 40.4, 37.2 and 20.8mgkg−1 for zinc. The lead, mercury and arsenic concentrations in meat and organs may be regarded as low, but the concentrations of cadmium in kidney and livers are sometimes relatively high. Apart from cadmium, lead and selenium, tissue trace element concentrations were not related to the age of the investigated animals. Differences in essential and non-essential trace element accumulation in sheep reared in different regions (states and territories) of Australia were also evaluated. Cadmium, lead and selenium were the only elements that appeared to show significant regional differences. Overall the results show that concentrations of the elements considered are within current acceptable ranges.

Effects of tribasic copper chloride on growth, copper status, antioxidant activities, immune responses and intestinal microflora of blunt snout bream (Megalobrama amblycephala) fed practical diets

A study was conducted to investigate the effects of dietary tribasic copper chloride on growth, copper status, antioxidant activities, immune responses and intestinal microflora in blunt snout bream, Megalobrama amblycephala. Eight practical diets containing different levels of copper (0, 3, 6, 9, 25, 50, 100 and 150mg Cukg−1) from tribasic copper chloride were fed to blunt snout bream (31g of initial average body weight) in quadruplicate groups in outdoor cages. Growth, copper status, antioxidant activities, immune responses and intestinal microflora were analyzed after a 56-day feeding period. Weight gain and specific growth rates in fish fed diets supplemented with 3–6mg Cukg−1 were significantly higher than those in fish fed the control diet (which supplemented with 0mg Cukg−1) (p<0.05). Fish fed diets supplemented with 9mg Cukg−1 had significantly lower feed conversion ratio than fish fed the control diets (p<0.05). Copper concentrations in liver, kidney and intestine were significantly higher in fish fed diets with 50–150mg Cukg−1 than those in fish fed the control diet (p<0.05). Dietary copper at levels ranging from 9mgkg−1 to 100mgkg−1 significantly enhanced T-AOC activities (p<0.05). In addition, diets supplemented with 100–150mg Cukg−1 significantly increased activities of AKP and ACP (p<0.05). Intestinal bacterial community structures in fish fed diets supplemented with 6–150mg Cukg−1 were different from those in fish fed diets supplemented with 0–3mg Cukg−1. The study showed that diets supplemented with 3–6mg Cukg−1 could meet the copper requirements for blunt snout bream fed practical diets; diets supplemented with 9mg Cukg−1 could increase feed efficiency; diets supplemented with 100mg Cukg−1 could increase activities of AKP and ACP and affect intestinal microflora structure, though leading to a status of increasing copper accumulation in tissues.

Biological monitoring of heavy metal contaminations using owls

Iron, manganese, copper, lead and cadmium were measured in the livers, muscles, kidneys and bones of Eurasian Eagle Owls (Bubo bubo), Brown Hawk Owls (Nixos scutulata) and Collared Scops Owls (Otus lempiji) from Korea. Iron concentrations by tissue within species did not differ, but there were significant differences among tissues across all species. Manganese and copper concentrations in muscles, kidneys and bones, but not livers, differed among species and also differed among tissues in the three owl species. We suggest that manganese and copper concentrations from this study were far below the level associated with their toxicity. Lead concentrations significantly differed among all species for livers and bones, and among tissues for each species. Cadmium concentrations were significantly different among species for all tissues and among tissues in Eurasian Eagle Owls and Collared Scops Owls. For most samples, lead concentrations in livers and bones, and cadmium in livers and kidneys, were within the background levels for wild birds. For some Eurasian Eagle Owls and Collared Scops Owls, lead concentrations were at an acute exposure level, whilst lead concentrations were at a chronic exposure level in Brown Hawk Owls. Cadmium concentrations were at a chronic exposure level in all three owl species. Acute and chronic poisoning was significantly correlated between indicator tissues. We suggest that lead and cadmium contamination in Eurasian Eagle Owls may reflect a Korean source, Brown Hawk Owls may reflect Korean and wintering sites, and Collared Scops Owls may reflect breeding and/or wintering sites.

Cadmium, Copper, Iron, and Zinc Concentrations in Kidneys of Grey Wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada)

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

Effects of Formaldehyde Inhalation on Zinc, Copper and Iron Concentrations in Liver and Kidney of Male Rats

In the present study, adult Wistar albino male rats were exposed to formaldehyde at different periods (subacute and subchronic) and concentrations (5.0 and 10.0 ppm) in order to figure out the changes in the concentration of Zn, Cu and Fe. It was observed that the formaldehyde inhalation caused gradual decline of body weights in the experimental groups when compared with control groups. It was found that subacute (4-week) or subchronic (13-week) exposure to formaldehyde for rats may cause growth retardation. After inhalation procedure, concentration of copper, zinc and iron were determined in liver and kidney tissues of rats using atomic absorption spectrophotometer. In addition, concentrations of Cu, Zn and Fe changed by the effect of formaldehyde in subacute and subchronic groups.

Acute and/or chronic contaminations of heavy metals in shorebirds from Korea

Zinc, copper, lead and cadmium were measured in the livers, kidneys and bones of Terek Sandpipers (Xenus cinereus), Great Knots (Calidris tenuirostris) and Red-necked Stints (Calidris ruficollis) from the Okgu Mudflat, Korea. Zinc concentrations in bones were significantly higher in Terek Sandpipers than the other two species and differed among tissues in Terek Sandpipers. Copper concentrations in kidneys and bones but not livers differed among species. Copper concentrations in Terek Sandpipers and Great Knots differed among tissues. Zinc and copper concentrations from this study were similar to those reported for other shorebirds. Lead concentrations significantly differed among all species for each tissue and among tissues for each species. Cadmium concentrations were significantly different among species for all tissues and among tissues in Great Knots and Red-necked Stints. In Red-necked Stints, lead and cadmium concentrations in each tissue were higher than the background levels for wild birds and both metals were considerably greater that reported previously for shorebirds. Cadmium concentrations in Terek Sandpipers and Great Knots were similar to concentrations reported in other shorebirds. In Terek Sandpipers and Great Knots, lead concentrations showed chronic exposure but not in Red-necked Stints. Cadmium concentrations showed chronic exposure in all three shorebird species.

Aluminum exposure through the diet: Metal levels in AβPP transgenic mice, a model for Alzheimer's disease

Aluminum (Al), iron (Fe), copper (Cu), and zinc (Zn) cause have been implicated in the etiology of certain neurodegenerative disorders. Moreover, these elements cause the conformational changes of Alzheimer's amyloid β protein. In this study, we determined the concentrations of Al, Cu, Zn, Fe, and Mn in various tissues of Tg 2576 (AβPP transgenic) Al-treated mice. Female Tg 2576 mice and wild-type littermates were exposed through the diet to 1 mg Al/g for 6 months. At 11 months of age, metal concentrations were measured in various tissues. In brain, Al levels were higher in hippocampus than in cortex and cerebellum. In hippocampus, Cu concentrations decreased in non-treated Tg 2576 mice, while Zn levels were higher in Al-treated mice. Copper, Zn, Mn and Fe concentrations in liver, kidney and bone were not affected by Al exposure. The current results show that Al exposure of Tg 2576 and wild-type mice did not produce important metal changes related with the genotype, responding similarly both groups of animals. As Tg 2576 mice have been considered as a potential model for Alzheimer's disease (AD), the present results would not support the hypothetical role of Al in the etiology of AD.

Copper toxicosis in a dairy goat herd

A closed herd of 400 mixed-breed dairy goats was examined because of a decrease in milk production and increase in mortality rate. Nine animals had died within a 1-month period. Clinical signs were evident only in lactating goats and included anorexia and recumbency. In the most severely affected goats, signs progressed to neurologic abnormalities and death. Serum aspartate aminotransferase activity, gamma-glutamyltransferase activity, and total bilirubin concentration were high in clinically affected does, but no evidence of hemolysis was found. A diagnosis of copper toxicosis was made on the basis of high liver and kidney copper concentrations and histologic evidence of hepatic necrosis. Goats were found to have been fed a mineral mix containing 3,050 ppm copper for 9 months prior to the onset of copper toxicosis. Overall, there was no consistent relationship between serum hepatic enzyme activities, serum copper concentration, and liver copper concentration. Clinically affected goats were treated with penicillamine, ammonium molybdate, sodium thiosulfate, and vitamin E. Penicillamine increased urine copper excretion in treated does versus untreated control animals. An increased incidence of infectious disease was identified in the herd 9 months later. Liver vitamin E concentration was low in 10 of the 12 goats that underwent necropsy. Findings suggested that penicillamine may be an effective treatment for goats with copper toxicosis. Production losses months after the diagnosis was made suggested that the intoxication had a prolonged animal welfare and economic impacts.

Effects of Dietary Arsenic Levels on Serum Parameters and Trace Mineral Retentions in Growing and Finishing Pigs

This experiment was conducted to investigate the effect of dietary arsenic (As) levels on growth performance, serum biochemistry, and the retention of iron, copper, and zinc in tissues of growing and finishing pigs. Ninety-six crossbred pigs were randomly allotted to four dietary treatments. The corn-soybean basal diets were supplemented with 0, 10, 20, and 30 mg As/kg. Arsenic trioxide was used as the arsenic source. The feeding experiment lasted for 78 d. The results showed that the high arsenic diet decreased average daily gain (ADG) (p<0.05) and increased feed gain ratio (F/G) (p<0.05). Arsenic intake significantly increased (p<0.05) serum gamma-gultamyltransferase (GGT), glutamic-pyruvic transaminase (GPT), and alkaline phosphatase (ALP) activities, and decreased (p<0.05) total protein, urea nitrogen, creatinine, and triglycerides. Glutamic-oxalacetic transaminase (GOT) activity, albumin, and cholesterol were not affected (p>0.05). Arsenic feeding elevated (p<0.05) liver and kidney copper concentration, but reduced (p<0.05) copper concentration in heart, bile, and lymphaden of intestine mesentery. There were increases in iron levels in liver, bile, spleen, thymus, and pancreas in pigs fed the high As diets (p<0.05), but iron contents in kidney, heart, and serum were decreased by the arsenic treatment (p<0.05). Zinc concentrations were increased (p<0.05) in liver, kidney, and thymus of pigs with arsenic treatment, but decreased (p<0.05) in bile and lymphaden of intestine mesentery. This study suggested that high dietary As levels could alter serum biochemical parameters and the retention of copper, iron, and zinc in the viscera of growing and finishing pigs.

Copper Transport Protein (Ctr1) Levels in Mice Are Tissue Specific and Dependent on Copper Status

Studies were conducted to determine distribution of the copper transporter, Ctr1, a transmembrane protein responsible for cellular copper uptake, in adult mice and in suckling mice nursed by either copper-adequate (Cu+) or copper-deficient (Cu-) dams. Western immunoblot analyses, using immunopurified antibody, detected monomeric (23 kDa) and oligomeric forms of Ctr1 in the membrane fraction of several mouse organs. Immunohistochemical analyses detected abundant Ctr1 protein in liver canaliculi; kidney cortex tubules; small intestinal enterocytes; the choroid plexus and capillaries of brain; intercalated disks of heart; mature spermatozoa; epithelium of mammary ducts; and the pigment epithelium, outer limiting membrane, and outer plexiform layer of the retina. Duodenal Ctr1 distribution was different in the adult compared with suckling mice; adult mice demonstrated strong intracellular staining of the enterocyte, whereas apical staining predominated in suckling mice. In Cu- mice at postnatal d 16 (P16), Ctr1 staining was augmented in kidney, duodenum, and choroid plexus, compared with Cu+ mice. Brain immunoblot data indicated that Ctr1 protein in membrane fractions of Cu- mice was 56% higher than Cu+ mice. Cu- mice had lower hemoglobin (56% of Cu+), and lower copper concentration (% of Cu+) in liver (15%), brain (26%), and kidney (65%). These results suggest that Ctr1 protein is expressed in multiple tissues and found in higher levels in selected organs after perinatal copper deficiency. Enhanced Ctr1 levels and redistribution might compensate in part for the decrease in copper supply. Mechanisms for the enhancement in Ctr1 staining remain to be established.

Seasonal and locational effects on serum, milk, liver and kidney chromium, manganese, copper, zinc, and iron concentrations of dairy cows.

Chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations were quantified in serum (n = 112), milk (n = 112), liver (n = 70), and kidney samples (n = 67) of dairy cows from an iron-steel processing region (Payas-Iskenderun) and from an area free of industrial pollution (Antakya) in Hatay, located in Southern Turkey. Samples were collected in the summer and winter and element determinations were carried out by inductively coupled plasma-atomic emission spectrometry. The mean concentrations of selected elements in serum were found to be similar in both regions. Milk samples collected from the nonindustrial region in the summer had higher Cr, Mn, and Zn concentrations than the polluted region. The liver Cu and kidney Mn levels of samples taken from the industrial region in winter were higher than samples of the unpolluted region. Copper and Fe concentrations in milk, Cr, Mn, Zn, and Fe levels in the liver, and Cr, Cu, Zn, and Fe levels in kidney samples were not found to be different among the regions in both seasons. Copper concentrations were below the critical level in the 25% of serum and 32% of liver samples analyzed in this study. Fifteen percent of serum samples and most of the liver samples had lower amounts of Zn than other reported studies. Although slight differences were observed between the industrial and nonindustrial regions, industrial activities and seasonal changes had no significant effect on selected element concentrations on cows and their milk.

Dietary sodium inhibits aqueous copper uptake in rainbow trout(Oncorhynchus mykiss)

Ours is the first study to demonstrate an influence of dietary sodium on waterborne copper uptake in fish. We examined possible interactions between dietary sodium and the response of freshwater rainbow trout (Oncorhynchus mykiss) to waterborne copper in light of recent evidence of interactions between sodium and copper metabolism in the gills. Trout were maintained for 6 days on one of four diets of increasing sodium concentration (0.25 mmol g(-1), 0.51 mmol g(-1), 0.76 mmol g(-1) and 1.27 mmol g(-1), which corresponds to 0.6%, 1.2%, 1.8% and 3% sodium by mass, respectively). At the end of 7 days, fish were exposed for 6 h to waterborne copper spiked with (64)Cu to determine if the dietary sodium affected responses to a subsequent short-term waterborne copper exposure. The radiotracer allowed us to distinguish between Cu occurring in fish tissues before the experiment and 'newly accumulated' Cu arising from the experimental exposure. Dietary sodium concentrations of 1.8% or 3% reduced newly accumulated copper concentrations in gill (from 93.9 ng g(-1) in control to 38.9 ng g(-1) and 20.0 ng g(-1) in fish fed 1.8% or 3% Na(+)-supplemented diets, respectively), liver (from 64.3 ng g(-1) to 23.1 ng g(-1) and 7.5 ng g(-1), respectively), kidney (from 29.3 ng g(-1) to 11.7 ng g(-1) and 7.8 ng g(-1), respectively), plasma (from 64.7 ng g(-1) to 21.5 ng g(-1) and 10.7 ng g(-1), respectively) and gut (from 6.8 ng g(-1) to 3.4 ng g(-1) and 2.2 ng g(-1), respectively) by 50.0-88.2%. The 3% Na(+)-supplemented diets also increased plasma and gut sodium concentrations by 38.1% (from 137.1 micromol g(-1) to 189.3 micromol g(-1)) and 104.3% (from 56.5 micromol g(-1) to 115.4 micromol g(-1)), respectively, relative to fish maintained on untreated diets. Whole body uptake rates of both sodium and copper were significantly reduced, and highly correlated (r=0.97) with one another, in fish fed high-sodium diets relative to controls. Moreover, sodium efflux was 12% and 38% higher in fish fed 1.8% and 3% sodium-enriched diets, respectively. Fish fed high-sodium diets also drank more water, but the contribution of drinking to waterborne copper uptake was negligible. From these results, we speculate that, at least in part, aqueous sodium and copper share a common branchial uptake route, probably through an apical sodium channel. According to this hypothesis, as the channel is downregulated with increasing internal sodium concentrations, both sodium and copper uptake from the water are inhibited.

Cadmium, copper and zinc in tissues of deceased copper smelter workers

Workers at a copper and lead smelter in northern Sweden have a multifactorial exposure to a number of heavy metals. The concentrations of cadmium, copper and zinc in liver, lung, kidney and brain tissues have been determined by atomic absorption spectrometry in 32 deceased long-term exposed male lead smelter workers, and compared with those of 10 male controls. Furthermore, copper and zinc levels in hair and nails were determined by energy-dispersive X-ray fluorescence. The highest cadmium concentrations among both workers and controls were observed in kidney, followed in order by liver, lung and brain. The levels in kidney, liver and lung were all significantly higher in the workers than in the controls (p < 0.03). Among the workers relatively strong positive correlations (p < 0.03) were observed between cadmium concentrations in liver and lung, liver and kidney, liver and brain, and lung and brain. In the exposed workers a positive correlation was observed between cadmium and zinc concentrations in the kidney (r s = 0.38; p = 0.034). This is probably mainly due to the protein metallothionein, which is stored in the kidney, binding equimolar amounts of these two metals. The highest concentrations of copper were found in hair and nails among both workers and controls, followed in order by liver, brain, kidney and lung. The tissue concentrations of copper in brain, lung and kidney were all significantly higher among the smelter workers than in the controls (p ≤ 0.036). Copper levels in lung and age at time of death were positively correlated among the exposed workers (r s = 0.39; p = 0.029). In the same group, positive correlations between copper and zinc concentrations in kidney (r s = 0.45; p = 0.009) and nails (r s = 0.68; p < 0.001) were also observed, reflecting possible biological interactions between these two metals. Among both workers and controls, the highest zinc concentrations were found in hair, followed in order by nails, liver, kidney, brain and lung. Significantly higher tissue concentrations among the workers as compared with the reference group were noted in kidney, liver and brain (p ≤ 0.033). Neither copper nor zinc concentrations in hair and nails seemed to provide a useful measure of the trace element status of the smelter workers.

Administration of the Oral Antibiotic Frenolicin-B Selectively Alters Copper Nutriture in Male Rats

The polyketide antibiotic Frenolicin-B (FB) produces anorexia and esophageal epithelial hyperplasia (EH) in rats, findings that are characteristic of zinc deficiency. Because FB also chelates divalent cations in vitro, we conducted studies to determine whether FB modifies blood and organ concentrations of zinc and other essential metals (calcium, copper, iron and magnesium). Groups of male Sprague-Dawley rats ( approximately 250g; n = 20/group) consumed diets with adequate (40 microg/g), deficient (<2 microg/g) or fortified (100 microg/g) zinc concentrations ad libitum for 28 d. Two groups fed either Zn-adequate or Zn-fortified diets also were given 100 mg/(kg. d) of FB in diet, and 2 groups were pair-fed controls. Histopathology or metal analyses were performed on tissues from 10 rats/group. FB caused EH of the nonglandular stomach but not of other tissues. Of the metals evaluated, only copper concentrations were significantly reduced in all tissues examined except kidney. A broad range of kidney copper concentrations was found; these concentrations were associated with plasma copper and proteinaceous deposits within tubules. In rats, FB substantially and selectively depletes Cu in vivo, suggesting that drugs with structures that permit metal chelation should be evaluated for their potential to alter trace metal nutriture.

Accumulation, distribution and toxicology of dietary nickel in lake whitefish ( Coregonusclupeaformis) and lake trout ( Salvelinusnamaycush)

An 18-day experiment was conducted to investigate the uptake and sublethal toxicity of dietary Ni in adult lake whitefish (LWF, Coregonus clupeaformis) and lake trout (LT, Salvelinus namaycush) fed diets containing 0, 1000 and 10 000 μg Ni/g, prepared with and without brine shrimp. The results of this experiment were used to design an experiment of longer duration in which one of the fish species was selected and exposed to lower dietary Ni doses. In the present study feed refusal was observed in LT and LWF fed 10 000 μg Ni/g, after three and 4–5 feedings, respectively. LT fed Ni-contaminated diets exhibited different patterns of Ni accumulation than LWF. Increased Ni concentrations in all LWF tissues, except the intestine, were associated with increased doses of Ni. Copper and Zn concentrations in kidney and liver of LWF were altered. Metallothionein concentrations in kidneys of LT fed 1000 μg Ni/g and 10 000 μg Ni/g and LWF fed 10 000 μg Ni/g and in livers of LWF fed 10 000 μg Ni/g (diet without shrimp only) increased significantly. Increased lipid peroxide production in the plasma of LT fed 10 000 μg Ni/g was observed. Blood glucose and electrolytes were affected by Ni exposure. Histopathological alterations were observed in kidneys of LWF fed low and high dose diets, livers of whitefish fed high dose diets, and intestines of LWF fed high dose diets and LT fed low and high dose diets. LT fed high dose diets exhibited significant decreases in weight.

High arsenic intake raises kidney copper and lowers plasma copper concentrations in rats.

The effect of high arsenic intake on copper metabolism was investigated. Male rats aged 6 wk had free access to purified diets containing either 0 or 100 mg As/kg diet and demineralized water for a period of 2 wk. Arsenic was added to the diet in the form of NaAsO2. The high-arsenic diet decreased feed and water intake and body weight gain, but significantly increased liver weight. Kidney weight was not affected. Arsenic feeding drastically elevated kidney copper concentration, but significantly reduced copper concentration in plasma. Both true absorption and biliary excretion of copper were decreased significantly in rats fed the high-arsenic diet. True copper absorption was lowered essentially through the lower copper intake in the rats fed arsenic. It is speculated that arsenic feeding primarily leads to copper accumulation in the kidney, followed by a decrease in feed intake and thus in true, absolute copper absorption, a decrease in plasma copper concentration, and a decrease in biliary copper excretion.

Measurement and Correlation of Liver, Kidney and Plasma Copper Concentrations and Haemoglobin in Holstein Cattle

Badiei, K. and Darboui, M. 1999. Measurement and correlation of liver, kidney and plasma copper concentrations and haemoglobin in Holstein cattle. J. Appl. Anim. Res., 15: 131–136. Haemoglobin, liver, kidney and plasma copper concentrations were measured in 40 Holstein cattle (20 bulls and 20 non-pregnant cows) aged, between 3 to 4 years in Fars Industrial Meat Complex. The mean copper levels as measured by atomic absorption flame spectrophotometry in liver, kidney and plasma were 57.97, 7.04 and 1 ppm, respectively. There were no significant differences between the two sexes (P>0.05). There was a low correlation (r= 0.19, P<0.05) between liver and plasma copper concentration. The correlation between the copper concentration of plasma and kidney was (r = 0.20, P<0.05). Although there was a significant correlation between haemoglobin and plasma copper concentration it could, not be explained.