Effect Of Dietary Copper Deficiency Research Articles

Protein Carbonyl, Lipid Peroxidation, Glutathione and Enzymatic Antioxidant Status in Male Wistar Brain Sub-regions After Dietary Copper Deficiency.

Copper a quintessential transitional metal is required for development and function of normal brain and its deficiency has been associated with impairments in brain function. The present study investigates the effects of dietary copper deficiency on brain sub-regions of male Wistar rats for 2-, 4- and 6-week. Pre-pubertal rats were divided into four groups: negative control (NC), copper control (CC), pairfed (PF) and copper deficient (CD). In brain sub regions total protein concentration, glutathione concentration and Cu-Zn SOD activity were down regulated after 2-, 4- and 6weeks compared to controls and PF groups. Significant increase in brain sub regions was observed in protein carbonyl and lipid peroxidation concentration as well as total SOD, Mn SOD and catalase activities after 2-, 4- and 6weeks of dietary copper deficiency. Experimental evidences indicate that impaired copper homeostasis has the potential to generate reactive oxygen species enhancing the susceptibility to oxidative stress by inducing up- and down-regulation of non-enzymatic and enzymatic profile studied in brain sub regions causing loss of their normal function which can consequently lead to deterioration of cell structure and death if copper deficiency is prolonged.

Erythrocyte Morphology, Osmotic Fragility and Hematological Studies after Short Term Dietary Copper Deficiency in Male Wistar Rats

Trace element copper is involved in myriad of physiological activities vital for normal function of organs of animals and humans from fetal development onwards. Its deficiency might occur in infants, children as well as adults and has been reported as a global problem affecting developed and undeveloped countries. Copper is essential for efficient iron uptake and mobilization. The present study evaluates the effect of dietary copper deficiency on erythrocyte of prepubertal male Wistar rats for 2, 4 and 6 w. Erythrocyte morphology, osmotic fragility, hematological parameters-hemoglobin, total leukocyte count, cell count (neutrophil, lymphocytes monocytes, eosinophils, platelets), packed cell volume, total red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were evaluated. Occurrence of stomatocytes, echinocytes, dracocytes, acanthocytes, Howell-Jolly inclusion, microcyte and macrocytes were observed after 2 and 4 w of copper deficiency when compared with their respective control and pair fed groups. The extent of morphological changes enhanced after 6 w of dietary copper deficiency with additional appearance of fragmented cells and few elongated cells. The percentage of altered erythrocyte morphology after 2 w deficiency was 0.051 % which enhanced subsequently as duration increased to 0.081 % (4 w) and 0.1709 % (6 w). Consequent to these changes significant (p<0.05) increase in erythrocyte osmotic fragility, eosinophil and lymphocyte count was observed while hemoglobin, neutrophil and platelet count, packed cell volume, total red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration decreased. Monocyte decrease was not significant. These changes were more pronounced after 4 and 6 w. Dietary copper insufficiency caused impairment of membrane, deregulation of hematopoiesis and altered the hematological profile indicating detrimental changes in properties of cellular membrane which may probably be due to enhanced oxidative stress.

Effects of dietary copper deficiency on adipocyte functions in a rat model of high-fructose diet-induced obesity

Background High fructose intake has been reported to impair copper (Cu) status, leading to low Cu availability with exacerbation of Cu-deficiency complications. These Cu–fructose interactions have been well documented in rats. Aims This experimental study was designed to evaluate the effects of dietary Cu deficiency on lipid profile in addition to adipocyte functions in the form of adiponutrin level and antioxidant capacity in a high-fructose diet-induced obesity rat model. Materials and methods The study was conducted on 60 male albino rats that were divided randomly into four equal groups as follows: group I (control group), group II (Cu-deficient group), group III (high fructose group), and group IV (Cu-deficient/high-fructose group). Plasma Cu level was measured by inductively coupled plasma optical emission spectrometry. Plasma ceruloplasmin and adipose tissue superoxide dismutase activities were assayed calorimetrically. Adiponutrin level in adipose tissue was measured by enzyme-linked immunosorbent assay. Results Plasma Cu level, ceruloplasmin activity, and adipose tissue superoxide dismutase activity were significantly decreased in Cu-deficient/high-fructose group when compared with other studied groups. However, adiponutrin level in adipose tissue was significantly increased in Cu-deficient/high-fructose group compared with other studied groups. Conclusion The modulated adiponutrin level, oxidative stress, dyslipidemia, and adipose tissue inflammation were highlighted as the principal culprits mediating Cu-deficiency and high-fructose diet complications such as nonalcoholic steatohepatitis.

Differential effects of dietary copper deficiency and excess on lipid metabolism in yellow catfish Pelteobagrus fulvidraco.

The present study was conducted to investigate the effects and mechanism of dietary Cu deficiency and excess on lipid metabolism in the liver, muscle and VAT of juvenile Pelteobagrus fulvidraco. To this end, yellow catfish were fed 0.76 (Cu deficiency), 4.18 (adequate Cu) and 92.45 (Cu excess) mg Cu kg(-1) diet, respectively, for 8 weeks. WG and SGR in the adequate Cu group were significantly higher than those in Cu deficiency and excess groups. In liver, Cu deficiency showed no significant effect on Cu and lipid contents, the activities of 6PGD, G6PD and FAS, and the mRNA levels of many tested genes, including 6PGD, G6PD, FAS, ACCα, PPARγ, LXR, HSL, PPARα and ATGL. Cu excess induced Cu accumulation, reduced the lipid content, FAS activity as well as the mRNA levels of 6PGD, G6PD, FAS, ACCα, PPARγ, HSL and ATGL. In muscle, dietary Cu levels showed no significant effects on lipid content, the activities of lipogenic enzymes and the mRNA levels of the most tested genes, including of 6PGD, G6PD, FAS, SREBP-1, PPARγ, HSL and LPL. In VAT, Cu and lipid contents, FAS activity, and the mRNA levels of 6PGD, G6PD, FAS, SREBP-1, LXR, PPARα and LPL were not significantly influenced by dietary Cu levels. Thus, the change of lipid contents among tissues could be related to the enzymatic activities and gene expression related to lipid metabolism. Different response patterns of enzymatic activities and gene expression in various tissues following dietary Cu levels indicated the tissue-specific regulatory effect by Cu.

Copper deficient rats and mice both develop anemia but only rats have lower plasma and brain iron levels

Iron homeostasis depends on adequate dietary copper but the mechanisms are unknown. Mice ( Mus musculus) and rat ( Rattus norvegicus) offspring were compared to determine the effect of dietary copper deficiency (Cu−) on iron status of plasma, liver, brain and intestine. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu− diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 13 and 32. Cu− rat and mouse pups were both anemic, but only rat pups had lower plasma and brain iron levels. Plasma iron was lower throughout the suckling period in Cu− rats but not Cu− mice. Cu− mice derived from dams restricted of Cu only during lactation were also severely anemic without hypoferremia. Intestinal metal analysis confirmed that Cu− pups had major reductions in intestinal concentration of Cu, increased Fe, and normal Zn. However, whole mouse (less the intestine) analysis demonstrated normal content of Fe indicating that the limitation in iron transport by intestinal hephaestin had no consequence to total iron reserves of the mouse. Further research will be needed to determine the reason Cu− mice were anemic since the “ferroxidase” hypothesis does not explain this phenotype.

Effect of dietary copper deficiency on iron metabolism in the pregnant rat

Cu and Fe metabolism are known to be linked, but the interactions during pregnancy are less well studied. In the present study we used rats to examine the effect of Cu deficiency during pregnancy on Fe and Cu levels in maternal and fetal tissue and on the gene expression profile of proteins involved in Cu and Fe metabolism in the placenta. Rats were fed diets with different Cu contents before and during pregnancy. Samples were collected on day 21 of gestation. Cu levels, ceruloplasmin activity and serum Fe all decreased in maternal serum of Cu-deficient animals. Maternal liver Fe inversely correlated with liver Cu. Placental Cu levels decreased with no change in Fe. Fe and Cu levels both decreased in the fetal liver. The drop in maternal liver Cu was significantly correlated with a decrease in organ weight of fetal liver, lung and kidney. No changes were observed in mRNA expression of Cu transporter 1, Menkes P-type Cu-ATPase 7A, Wilson P-type Cu-ATPase 7B, cytochrome-c oxidase, and Cu chaperone Atox1 in the placenta of Cu-deficient dams. Transferrin receptor 1 and the Fe-responsive element (IRE)-regulated divalent metal transporter 1 (DMT1) were up regulated; while ferroportin and non-IRE1-regulated DMT1 levels did not change. These data show that Cu deficiency during pregnancy not only has a direct effect on Fe levels but also regulates the expression of Fe transporters. The pattern closely mirrors that seen in Fe deficiency, suggesting that the changes are a consequence of the decrease in serum Fe, implying that the developing fetus not only suffers from Cu, but also from Fe deficiency.

Augmented metalloproteinase activity and acute lung injury in copper-deficient rats.

Dietary copper is required for normal function of >30 mammalian enzyme systems. Copper deficiency causes a number of cardiovascular defects as well as impaired immune cell function. Little is known regarding the effects of copper deficiency on acute inflammatory responses, but this topic is relevant because many members of the Western population receive less than the recommended dietary allowance of copper. In the current studies, we investigated the effects of dietary copper deficiency on acute lung injury induced by intrapulmonary deposition of IgG immune complexes. Weanling male Long-Evans rats were fed diets either adequate (5.6 microg/g) or deficient (0.3 microg/g) in copper. IgG immune complex lung injury was greatly increased in copper-deficient rats as determined by lung vascular leakage of albumin and histopathology. However, no change was observed in either the lung content of tumor necrosis factor-alpha or lung neutrophil accumulation. Lungs from copper-deficient rats had much higher levels of matrix metalloproteinase (MMP)-2 and MMP-9 than did copper-adequate control animals. This increased activity was not attributable to alveolar macrophages or neutrophils. These data suggest that the augmented lung injury caused by copper deficiency is due to increased pulmonary MMP-2 and MMP-9 activity and not a generalized amplification of the inflammatory response.

Cardiovascular effects of dietary copper deficiency.

Dietary copper deficiency may impair cardiovascular health by contributing to high blood pressure, enhancement of inflammation, anemia, reduced blood clotting and arteriosclerosis. The purpose of this review is to compile information on the numerous changes of the heart, blood and blood vessels that may contribute to these cardiovascular defects. These alterations include weakened structural integrity of the heart and blood vessels, impairment of the use of energy by the heart, reduced ability of the heart to contract, altered ability of blood vessels to control their diameter and to grow, and altered structure and function of circulating blood cells. The fundamental causes of these changes rest largely on reduced effectiveness of enzymes that depend on copper for their activity.

In Vivo Oxidative Modification of Erythrocyte Membrane Proteins in Copper Deficiency

Oxidative stress has been postulated to contribute to the pathology associated with dietary copper deficiency. In vivo, erythrocytes are probable targets of oxidative damage because they are exposed to high concentrations of oxygen and contain heme iron that can autoxidize, which results in the formation of superoxide anions. Activity of the important antioxidant enzyme, copper, zinc superoxide dismutase, decreases markedly in erythrocytes during copper deficiency. The effect of dietary copper deficiency on indicators of oxidative stress was examined in erythrocyte membranes of rats maintained on a purified copper-deficient diet for 35 days after weaning. Erythrocytes were separated into young and old populations on a Percoll gradient prior to membrane isolation and quantification of lipid peroxides and protein carbonyls. Protein carbonyls, determined by Western blot immunoassay, were detected predominantly in both the alpha and beta chains of spectrin. Alpha and beta subunits of spectrin in erythrocyte membranes from copper-deficient rats contained higher amounts of carbonyls than controls, regardless of the population of erythrocytes studied. This study suggests that spectrin may be a specific target for oxidative damage when erythrocyte copper, zinc superoxide dismutase activity is reduced by copper deficiency. Copyright © 1997 Elsevier Science Inc.

Feeding of 1,1,1-trichloro-2,2-bis( p-chlorophenyl)ethane (DDT) reduces some effects of dietary copper deficiency in rats

This study was conducted to examine the influence of dietary addition of 0.5g/Kg 1,1,1-trichloro-2,2-bis( p-chlorophenyl)ethane (DDT) on the effects of dietary copper deficiency in rats. Copper-deficient diet lowered tissue copper concentrations, elevated liver iron concentration, enlarged heart size, caused anemia, reduced plasma ceruloplasmin activity, and elevated levels of thiobarbituric acid reactive substances (TBARS, an indicator of oxidative stress), in liver, heart and intestinal mucosa. Although DDT feeding had no influence on tissue concentrations of copper and iron, it significantly suppressed the cardiac enlargement and elevation of TBARS levels in intestinal mucosa caused by copper-deficient diet, and elevated tissue levels of ascorbic acid. In addition, DDT feeding tended to reduce other variables associated with dietary copper deficiency, including the levels of blood hemoglobin and TBARS in liver and heart. DDT. These results indicate that DDT feeding reduces some effects of copper deficiency.

Effects of dietary copper deficiency on relative food intake and growth efficiency in rats

Weanling male rats were fed either copper-adequate (CuA) or copper-deficient (CuD) diets ad lib for 20 wk. A pair-fed group was also studied. Two relative food intake indices (RFIs) and a growth efficiency (GE) index were calculated. Body weights of the CuD group became reduced compared to the CuA group starting the sixth week of the study. Copper deficiency was found to affect both of the RFI indices and the GE index in a time-dependent manner. RFIs and GE were reduced early, but recovered towards the control values during the last half of the experimental period. At the end of 20 wk, organ copper content and serum ceruloplasmin was reduced in the CuD group. Dietary copper deficiency reduces growth rate through effects both on food intake and efficiency of food utilization for growth.

Cystine feeding enhances defects of dietary copper deficiency by a mechanism not involving oxidative stress

Dietary cystine supplementation exacerbates the effects of dietary copper deficiency. We examined the possibilities that this exacerbation is caused by an oxidative mechanism or by an effect on copper status. Male Sprague-Dawley rats (∼ 120 g) were fed copper-adequate or copper-deficient diets (0.5 or 16 mg/kg diet) that were supplemented with combinations of l-cystine (20 g/kg diet), vitamin E (37 mg/kg diet), and sodium tungstate (360 mg/L in drinking water). Dietary copper deficiency depressed serum and organ copper concentrations; increased heart size; caused anemia; reduced heart and liver superoxide dismutase and cytochrome c oxidase activities; and increased serum, heart, and liver thiobarbituric acid reactive substances. Cystine feeding exacerbated the cardiac enlargement and anemia of copper deficiency and reduced liver cytochrome oxidase and superoxide dismutase activities, but had no effect on organ copper content. Cystine feeding had no effect on serum or heart thiobarbituric acid reactive substances but depressed liver thiobarbituric acid reactive substances production. Neither vitamin E nor tungsten, which was used to inhibit sulfite oxidase and its potential production of free radicals, had an effect on the copper- or cystine-dependent changes in heart size, hematocrit, or hemoglobin. Dietary vitamin E and tungsten had variable beneficial effects on copper- and cystine-dependent changes in variables related to red blood cell size, but these effects could not be consistently related to the inhibition of TBARS production caused by vitamin E and tungsten. We conclude that, while cystine feeding enhanced signs of copper deficiency, it did not do so by an oxidative mechanism or by altering copper status.

Dietary copper deficiency reduces heat shock protein expression in cardiovascular tissues

Dietary copper deficiency impairs cardiovascular function by depression of catecholamine metabolism, and alteration of the structure and function of cardiac mitochondria. Heat shock proteins (HSPs) are a group of cellular homeostatic proteins that are induced in vascular tissue by catecholaminergic transmission after exposure to stress. We investigated the effects of dietary copper deficiency on the induction and accumulation of HSPs in several cardiovascular tissues. Stress-induced levels of aortic HSP70 mRNA were reduced in copper-deficient (CuD) rats when compared with copper-adequate (CuA) controls. Cocaine-induced HSP70 mRNA accumulation was not different between CuA and CuD rats, suggesting that reduced HSP70 levels in restrained CuD animals may result from altered catecholaminergic neurotransmission. The level of HSP60 mRNA was specifically reduced in the atria of CuD rats, which may be associated with altered mitochondrial structure and function. These results describe a novel relationship between dietary copper deficiency and the expression of highly conserved cellular stress response proteins. Loss of these essential homeostatic proteins in vascular tissue may contribute to the impairment of cardiovascular function known to accompany copper deficiency.

Hyperbaric hyperoxia exaggerates respiratory membrane defects in the copper-deficient rat lung.

Scanning (SEM) and transmission electron microscopy (TEM) were used to examine the effect of dietary copper deficiency and hyperbaric hyperoxia, alone and in combination, on lung structure. Male, weanling Sprague-Dawley rats were fed a copper-deficient (CuD, 0.2 microgram/g) or copper-adequate diet (CuA, 5.1 micrograms/g). After 35-41 d on their respective diets, rats from each group were placed inside a pressure vessel kept at 27 degrees C under one of two pressure protocols. Air controls were maintained at 1 atm for 75 min. Rats exposed to oxygen were maintained at 1 atm of air plus 3 atm of oxygen for 1 h and then decompressed for 15 min. Under SEM, none of the treated lungs (CuD, CuA-O2 exposed, or CuD-O2 exposed) showed abnormal lung morphology from the conducting bronchioles down to the alveoli. Copper-deficient red blood cells were abnormally shaped. Under TEM, CuA-O2-exposed lungs showed thicker respiratory membranes, especially basement membranes and endothelial cells, and alveolar Type II cells having more than the usual number of surfactant vacuoles. CuD lungs also showed thicker endothelial and basement membrane components of the respiratory membrane, but normal looking Type II cells. CuD-O2-exposed lungs showed greatly thickened respiratory membranes and severe disruption of both endothelium and basement membrane and, judging by the increased number of nuclei per field, an increase in the number of both Type I and Type II cells. We conclude that copper deficiency enhances the damage caused by O2 toxicity, an effect that may be caused by reduced antioxidant status.

Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion.

Effects of copper deficiency on T-cell mitogenic responsiveness and phenotypic profile of blood mononuclear cells from swine

Summary The effect of dietary copper deficiency on T-cell mitogenic responsiveness and phenotypic profile of blood mononuclear cells (mnc) in weaned pigs was examined. Outbred, weaned pigs were fed a semipurified diet containing adequate (6.4 mg/kg of body weight) or deficient (0.8 mg/kg) amounts of Cu. Pigs fed the low Cu diet for 10 weeks had markedly decreased concentrations of Cu in liver and plasma, and hypertrophic hearts. In vitro reactivity of mnc from Cu-deflcient pigs to phytohemagglutinin and concanavalin A was significantly suppressed. This functional impairment was not associated with a decrease in the percentages of T cells, CD4 or CD8 cell subsets, or B cells. Expression of sla-dq and sla-dr class II major histocompatibility complex (mhc) antigens was increased by Cu deficiency, the former significantly. Unlike rodents, in which inadequate Cu nutriture induces functional T cell deficiency that is associated with a decrease in the CD4 T-cell subset, swine fed inadequate Cu diets for 10 weeks had no changes in mhc subsets yet clearly manifested functional impairment of T-cell responses.

EFFECT FO DIETARY COPPER DEFICIENCY ON BRAIN CATECHOLAMINES OF NEWBORN RATS

To investigate the effect of dietary copper deficiency on brain catecholamines of newborn rats an experimental model was developed. Three groups of 10 female Sprague - Dawley rats were used. Group 1, copper deficient group, was fed with a copper-free diet 5 weeks prt-gestation and during gestation until delivery. Group II, the control, received a copper addecuate diet (6ppm). Group III, the pairfed, received a copper addecuate diet, but restringed according to the caloric input of the copper deficient group. Inmediatly after birth, the newborn rats from a total of 7; 4 and 7 litters of the groups I, II and III, respectively were decapited. Eleven assays of each group were performed. For each assay we used 1, 2, 3, or 4 whole brains minus cerebella. Whole brain dopamine and noradrenaline levels were quantified by high performance liquid chromatography with electrochemical detector. Copper deficient group showed a highly significant decrease in brain noradrenaline levels (50% lesser than others two groups: p = 0.0341), whereas dopamine concentrations remained largely unaltered. The levels of brain copper in the newborn rats in group 1 were significantively reduced (p = 0,0001) as well as brain weight (p = 0,0012). The CA1 sector neuronal counting was unaltered, however the girus dentatus counting showed a significant decrease in neuronal cellularity in Group I. We conclude that the materno-fetal copper deficiency altered the synthesis of noradrenaline. This could be a consequence of a functional impairment (possibly Dopamine - - hidroxilase enzyme dismiinished activity), however the possible role of the hypocellularity as the one observed in the girus dentatus sector can not be excluded.

The effects of dietary copper deficiency and psychological stress on blood pressure in rats

In each of two experiments, adult, male Sprague-Dawley rats were deprived of copper and were subjected to the chronic stress of close confinement. A 2 × 2 factorial design was used because both copper deficiency and stress have been implicated in the regulation of blood pressure and are implicated in a major consequence of human hypertension— ischemic heart disease. Copper deficiency was verified by a decrease in copper in several organs. Both copper deficiency and stress increased blood pressure; results were independent. Sodium in heart was increased by deficiency in both experiments, but was increased in brain in only the second experiment. The combination of stress and deficiency produced an increase in mortality in one of two experiments. A decrease in cholesterol in plasma due to stress is consistent with earlier data from rats but is in contrast to data from humans. Both stress and copper deficiency produce potentially adverse changes in cardiovascular physiology and the chemistry of brain, heart and other organs. These results may be germane to humans because stress is frequent and some diets are low in copper.

Respiratory Burst and Candidacidal Activity of Peritoneal Macrophages Are Impaired in Copper-Deficient Rats

To investigate the effect of dietary copper deficiency on the function of peritoneal macrophages, weaned male Lewis rats were pair-fed diets containing either adequate (7 mg/kg diet; +Cu) or deficient (0.7 mg/kg diet; -Cu) levels of copper for 5 wk. Cellular copper content and the activity of Cu, Zn superoxide dismutase were significantly lower in both resident and thioglycollate-elicited macrophages from -Cu rats than in cells from +Cu controls. Reduced cellular Cu status was associated with impaired respiratory burst as assessed by zymosan-induced chemiluminescent activity and superoxide anion (O2-) generation. Candidacidal activity of macrophages from -Cu rats was also reduced and was highly correlated with chemiluminescent activity and O2- generation. In contrast, phagocytosis of opsonized erythrocytes by peritoneal macrophages from -Cu rats was normal. Elicited peritoneal macrophages from marginally Cu-deficient rats also killed significantly fewer yeast cells than macrophages from +Cu rats. These results demonstrate that macrophage function is impaired by dietary Cu deficiency and that the candidacidal activity of these cells may provide a sensitive indicator of Cu status.

Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats

Dietary copper deficiency was produced in Swiss albino mice and Sprague Dawley rats to determine the organ specificity of alterations in norepinephrine (NE) and dopamine (DA) concentrations and the relationship with organ copper levels. A 5-week dietary treatment was used, which started 1 week after birth for mice, initially via dams, and 3 weeks after birth for rats. Mice offspring (6 weeks of age) and rats (8 weeks of age) maintained on a copper-deficient (−Cu) treatment were compared with copper-adequate (+Cu) controls. Compared with +Cu animals, −Cu mice and rats were anemic and had low (<1% of +Cu) ceruloplasmin activities but normal body weights. The −Cu mice had organ copper concentrations ranging between 30% and 65% of +Cu values for eight organs studied, with the thymus being the least depleted. For −Cu rats, the range was 15% to 65%. Significant reductions in NE concentration were observed in the heart, pancreas, and spleen of −Cu mice. Elevated DA levels were observed in all organs except the brain. For −Cu rats, the NE level was lower in the heart and the DA level was higher in both the heart and spleen compared with +Cu rats. Dopamine elevation in the heart and spleen for both −Cu mice and rats was four- and fivefold higher, respectively. Adrenal catecholamine levels were only slightly changed by copper deficiency in mice or rats. Urinary levels of both NE and DA were higher in −Cu rats and mice. Plasma and heart tyrosine levels were not altered in −Cu mice. Elevated DA in −Cu rodents may be due to limiting dopamine-β-monooxygenase. Higher urinary NE and lower organ NE may be due to a combination of decreased synthesis and enhanced turnover. The magnitude of decreased organ copper was not predictive of altered catecholamine pool size.