Effect Of Copper Deficiency Research Articles

Effect of copper-deficient diet on metabolism in rat auditory structures

Copper is a trace element known to be critical for normal brain function, and abnormal copper metabolism has been associated with some disorders involving the auditory system. We examined effects of copper deficiency on metabolism in major structures of the auditory system. Homogenates of cochlea, cochlear nucleus and inferior colliculus of rats, as well as whole brain, were assayed for activities of enzymes of oxidative and glycolytic energy metabolism — malate and lactate dehydrogenase, enzymes of acetylcholine metabolism - choline acetyltransferase and acetylcholinesterase, and concentrations of amino acids. Whole brain was also assayed for activity of Superoxide dismutase, a copper-containing enzyme, and concentrations of minerals. For these chemicals and tissues, the only significant differences between copper-deficient and copper-adequate rats were: (1) decreased copper and magnesium and increased potassium concentrations in whole brain of copper-deficient rats and (2) an elevation of glutamine concentration in inferior colliculus and whole brain of copper-deficient rats. The elevated glutamine could not be related to any change in activity of glutamine synthetase or glutaminase, major enzymes of glutamine metabolism. It is speculated that the increase in glutamine might result from a net increase in ammonia accumulation in the brains of copper-deficient rats.

Effect of copper deficiency on tissue, blood characteristics, and immune function of calves challenged with infectious bovine rhinotracheitis virus and Pasteurella hemolytica.

Fourteen Holstein steers, averaging 30 d of age, were fed a semipurified diet (1.5 mg of Cu/kg) supplemented with 0 (-Cu) or 10 mg of Cu/kg of diet (+Cu) for 5 mo. Calves were then challenged by consecutive exposure to aerosol preparations of infectious bovine rhinotracheitis virus (IBRV) and Pasteurella hemolytica on d 0 and 7, respectively, of the 30-d study. Serum ceruloplasmin and plasma copper were higher in +Cu calves throughout the challenge period and increased in +Cu calves after microbial challenge. Heart weights were higher in -Cu calves, although weights of liver, spleen, and thymus were not different between treatments. Copper concentrations in all tissues as well as thymus zinc were higher in +Cu calves. Serum immunoglobulin M tended to be higher in +Cu calves and increased in both treatments after IBRV challenge. Serum IBRV antibody titers were higher in -Cu calves with detectable seroconversion by d 10 postinfection. In contrast, antigen-specific antibodies to P. hemolytica tended to be higher in +Cu calves on d 21. Copper status did not affect blastogenic response, but phytohemagglutinin (PHA)-stimulated blastogenesis was higher in both treatments after IBRV challenge. Repletion of lymphocyte cultures with copper chloride increased proliferative responses to PHA in both +Cu and -Cu calves, and greater responses at all levels of copper (1 to 16 micrograms/mL) were noted in -Cu calves. These results indicate that copper deficiency affects various physiological characteristics that may be important in immunological defense to pathogenic challenge.

Effect of copper deficiency on the hepatic synthesis and rate of plasma release of cholesterol

The relative rates of hepatic 3H incorporation into digitonin-precipitable sterols (DPS) and release of labeled DPS into the plasma were compared between copper-deficient (CuD) and copper-adequate (CuA) rats. Following intravenous injection of 3H 2O and Triton WR 1339, the liver and plasma 3H-DPS radioactivities were measured at 2, 4, 6, and 8 hr, and the net total accumulation of plasma cholesterol (CH) and triglyceride (TG) was determined during the 8-hr period. In both groups, the liver synthesis of 3H-DPS displayed a biphasic curve, with an initial slow rate up to 4 hr, followed by a rapid increase starting at 6 hr. During the latter phase, a notable increase in liver 3H-DPS radioactivity was observed in CuD rats, but the plasma release of 3H-DPS did not significantly change, despite the increased synthesis of 3H-DPS in the liver. In both groups, the net total accumulation of CH in the plasma, as expressed in mmol CH/100 g body weight, increased steadily from 1.2 mmol at 2 hr to 4.7 mmol at 8 hr, while plasma TG accumulated at a much greater rate ranging from 3.3 mmol at 2 hr to 13.6 mmol at 8 hr. There was no significant difference in net total accumulation of CH or Tg in the plasma between the groups at any given interval. The results provide evidence that copper deficiency stimulates the liver synthesis of cholesterol, but that it does not result in an accelerated release of newly synthesized cholesterol from the liver involving very low density lipoproteins (VLDL). Thus, the present findings suggest that the hypercholesterolemia induced in copper deficiency is not attributable to a stimulation of the hepatic release of VLDL cholesterol into the plasma.

Respiratory Distress Syndrome in Copper Deficiency: An Experimental Model Developed in Rats

An experimental model has been developed to investigate the effect of copper deficiency on lung maturity in the newborn rat. Three groups of female Sprague-Dawley rats were used: the copper-deficient group was fed with a copper-free diet; the control group received a copper-adequate diet, and the pair-fed group was fed with a limited copper diet. After gestation and delivery, 35% of the newborn copper-deficient group showed respiratory distress syndrome (RDS). The neonatal lungs were isolated and processed for ultrastructural and biochemical study: A greater thickness of the air-blood barrier was observed in the lungs of the copper-deficient group, however, no other differences were observed in the rest of the pulmonary structures. Quantitative differences in pulmonary surfactant were not found in the three groups. The thickness of the air-blood barrier might explain the RDS observed in the copper-deficient newborns.

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.

Copper Deficiency Alters Vasodilation in the Rat Cremaster Muscle Microcirculation

The effects of copper deficiency on smooth muscle relaxation were studied in the cremaster muscle microcirculation. Male Sprague-Dawley rats were fed either a copper-adequate diet (CuA, 5 μg copper/g diet) or copper-deficient diet (CuD, no added copper) for 17–27 d before experimentation. In vivo television microscopy was used to quantify agonist-induced diameter changes in third-order arterioles. Endothelium-dependent relaxation, which is hypothesized to be mediated by nitric oxide, was attenuated by copper deficiency. Both receptor (acetylcholine, 10-7 to 10-4 mol/L) and nonreceptor (calcium ionophore A23187, 10-8 to 10-7 mol/L) relaxation was decreased. Nitric oxide-mediated dilation, which was endothelium-independent (10-7 to 10-5 mol/L sodium nitroprusside), was also attenuated by copper deficiency. Maximal responses were as follows: for acetylcholine, 136 ± 16% CuA vs. 45 ± 15% CuD; for A23187, 104 ± 16% CuA vs. 21 ± 11% CuD; and for nitroprusside, 125 ± 12% CuA vs. 46 ± 13% CuD. There was no difference in microvascular dilation between groups treated with 10-6 to 10-4 mol/L of the phosphodiesterase inhibitor papaverine (e.g., CuA 109 ± 11% vs. CuD 133 ± 21% with 10-4 mol/L). These results suggest that copper deficiency inhibits the nitric oxide-mediated mechanism of vascular smooth muscle relaxation without altering the capacity of the smooth muscle to relax. We suggest that copper deficiency either decreases nitric oxide radical availability or disrupts the nitric oxide-guanylate cyclase interaction.

Excess sulphur partially alleviates copper deficiency effects in mustard

Abstract Mustard (Brassica campestris L. var. sarson) cv. T42 was grown in refined sand at two copper levels, deficient (10−8 M) and normal (10−6 M), each at two molybdenum levels, normal (5×10−7 M) and excess (10−4 M), and two levels of sulphur, normal (2 × 10−3 M) and excess (4 × 10−3 M) with nitrate and ammonium nitrate as nitrogen sources. In mustard, excess sulphur interacted with copper deficiency when the supply of excess sulphur at adequate molybdenum levels partially alleviated the effects of copper deficiency namely, visible copper deficiency symptoms, decrease of dry weight, seed yield and the activity of cytochrome oxidase. The alleviation of copper deficiency effects by excess sulphur was also discernible at excess molybdenum levels. Excess S interacted with excess Mo in decreasing significantly the tissue Mo contents for both nitrogen sources. Excess S also significantly depressed the NR activity in the NO3 treatment at both levels of Mo supply, indicating the presence of an interaction betw...

Effect of copper deficiency on the plasma clearance of native and acetylated human low density lipoproteins

The rates of plasma clearance of human native low density lipoproteins (LDL) and acetylated human low density lipoproteins (acetyl-LDL) were compared between copper-deficient (CuD) and copper-adequate (CuA) rats. Purified human LDL (d 1.02–1.063) were labeled with 125I and injected to fasted recipient rats intravenously. At different time intervals plasma clearance of 125I radioactivity was measured. The percent of clearance was calculated based on the total plasma volume, as determined by a radioisotopic dilution method. Native human 125I-LDL were cleared at a faster rate in CuD, compared with CuA rats. The half-times (t 1 2 ) of 125I-LDL clearance are 4.90 ± 0.20 and 5.80 ± 0.30 hours in CuD and CuA rats, respectively. The plasma trichloroacetic acid-soluble 125I-radioactivity was significantly and steadily increased in CuD rats at each interval, reflecting the faster clearance and degradation of LDL in those rats. The plasma removal of 125I-acetyl-LDL was faster compared with that of 125I-LDL. The half-times (t 1 2 ) of acetyl-LDL in CuD and CuA rats are 5.20 ± 0.06 and 5.16 ± 0.08 minutes, respectively, with no significant difference between the groups. The data indicates that the uptake of LDL via the “scavenger” receptor remains unaffected in copper-deficient rats. The faster removal of the unmodified (native) LDL in CuD group suggests that the apoB,E receptor is up-regulated in copper-deficient rats and that the hypercholesterolemia observed in copper deficiency is not associated with the defective uptake of LDL by the apoB,E-receptor dependent mechanism.

Copper Uptake and Retention in Liver Parenchymal Cells Isolated from Nutritionally Copper-Deficient Rats

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 +/- 4 pmol Cu.mg protein-1.min-1 as compared with 30 +/- 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficient rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper-deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency.

The effect of copper deficiency on adriamycin toxicity

The effect of copper (Cu) deficiency on antioxidant status of liver and heart and its effect on adriamycin toxicity was assessed. Weanling rats were fed Cu-adequate (+Cu) and Cu-deficient (−Cu) diets for 3 weeks and then injected intraperitoneally once with saline or adriamycin (8 mg/kg). All − Cu rats had increased heart/body weight ratios compared to + Cu rats. Regardless of Cu status, adriamycin decreased body weight and increased heart cytochrome c oxidase, but had no effect on Cu.Zn-superoxide dismutase, glutathione peroxidase, the thiobarbituric acid (TBA) index or liver cytochrome c oxidase activity. − Cu, adriamycin rats had significantly decreased heart weights (0.54 + 0.02 g/kg body wt.) compared to − Cu, saline rats (0.69 ± 0.05 g/ kg body wt.). Four of 6 − Cu rats given adriamycin had abnormal EKGs, with 3 showing extrasystoles and 1 having a severe bradycardia. All + Cu rats given adriamycin had normal EKGs. Pathological changes detected with electron microscopy were most severe in − Cu rats given adriamycin.

Copper Deficiency in a Genetically Hypertensive Cardiomyopathic Rat: Electrocardiogram, Functional and Ultrastructural Aspects

The effect of copper deficiency on cardiac function and structure was studied in a strain of rats (SHHS/Mcc-cp) known to develop cardiac failure as adults. Restriction of dietary copper (less than or equal to 1 mg/kg vs. 6 mg/kg in adequate diets) at weaning in both sexes for a 6-wk period produced cardiac hypertrophy. Male rats developed more severe copper-deficiency symptoms than their female counterparts. In both sexes of copper-deficient rats, there was an increase in cardiac length, width, free ventricular wall thickness and septum thickness. Electrocardiographic tracings revealed greater QRS height among male copper-deficient rats. Heart rate also was substantially reduced in this group. The increased volume of myocardium occupied by mitochondria in the copper-deficient male rats might result in increased electrical resistance that would increase the QRS height; hypertrophy or anemia also could be contributory. Some male copper-deficient rats had prolongation of the QRS in a bundle branch block pattern. Maximal rates of rise and fall for left ventricular pressure were reduced in male copper-deficient rats. The gross histology indicated that this type of heart failure was more concentric than eccentric. The copper-deficient male rat may serve as a useful model for studying the concentric cardiac hypertrophy that occurs in humans.

Incorporation of tritiated water into sterol in copper-deficient rats

The effect of copper deficiency on absolute rates of cholesterol synthesis was investigated in the rat. Male weanling rats were fed semi-purified diets containing adequate (7.13 ppm) or deficient (0.621 ppm) levels of copper for 6 weeks. Copper-adequate and -deficient animals ( n = 6/group) were injected intraperitoneally with 50 mCi 3H-labelled water and killed 1 h post-injection. Copper-deficient animals had elevated heart weights and reduced body and spleen weights. Plasma cholesterol levels were significantly elevated and hematocrits were reduced. Absolute rates of carcass cholesterol synthesis per organ were 1.9-fold higher in copper-deficient rats ( P < 0.025). Previous studies have indicated that hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (E.C.1.1.1.34) activity is increased by copper deficiency; however, de novo synthesis of cholesterol from 3H-labelled water was not significantly elevated in the liver. The present data indicate that newly synthesized cholesterol exported to the plasma was increased 2.1-fold ( P < 0.01) in copper-deficient rats. Since it has been demonstrated that hepatic export of cholesterol is increased with copper deficiency and that the major tissue for export of newly synthesized cholesterol is the liver, we hypothesize that the origin of radiolabeled cholesterol in the plasma was the liver. These data support the hypothesis that elevated levels of hepatic HMG-CoA reductase seen with copper deficiency are associated with an increased rate of whole body and hepatic cholesterol synthesis.

Effect of copper deficiency on photosynthetic electron transport in wheat plants

Copper deficiency in wheat (Triticum aestivum L. cv. Nazareno Stramppeli) markedly affects photosynthetic activity. Flag leaves of copper‐deficient plants showed a 50% reduction of the photosynthetic rate expressed as mg CO2 dm−2h−1. The activities of PSI and PSII, determined for isolated chloroplasts, as well as fluorescence measurements on intact leaves of copper‐deficient plants, indicated a low activity of photosynthetic electron transport. Ribulose bisphosphate carboxylase/oxygenase (Rubisco) activity was not affected by copper deficiency but copper deficiency affected the chloroplast ultrastructure, especially at the level of grana, where a disorganization of thylakoids is evident.

Effect of copper deficiency on photosynthetic electron transport in wheat plants

Effect of copper deficiency on photosynthetic electron transport in wheat plants

Beer mitigates some effects of copper deficiency in rats

Because of an epidemiologic association of decreased risk of death from ischemic heart disease with moderate use of alcoholic beverages, and because numerous abnormalities found in people with ischemic heart disease are also found in animals deficient in copper, rats were fed a diet deficient in copper and were given either beer or water to drink. Rats drinking beer lived nearly six times as long and had lower plasma cholesterol, less cardiac enlargement, and higher liver copper. Apparent absorption and biological half-life of oral radiocopper were increased by beer. The effects were not attributable to alcohol, chromium, or copper in beer. Beer intakes were similar to those of some people in the United States. Results may explain seasonal cycles in plasma cholesterol and may be germane to the epidemiology of ischemic heart disease because diets in the United States seem to be low in copper.

Cardiovascular but not renal effects of copper deficiency are inhibited by dimethyl sulfoxide

Dietary copper (Cu) deficiency produces known defects in the kidney. We studied the effects of Cu deficiency on renal function and microvillar enzyme activity. Because Cu deficiency causes oxidative damage in other tissues and because of recent success in preventing cardiovascular defects of Cu deficiency with antioxidants, we also studied the effect of the hydroxyl radical (OH) scavenger, dimethyl sulfoxide (DMSO), on observed renal changes of Cu deficiency. Male, weanling Sprague-Dawley rats were fed, in a 2×2 design, diets deficient in Cu (CuD) or supplemented with Cu (CuS, 5 ppm) and water with or without DMSO (4.75%) for 35 days. Cu deficiency in CuD rats was confirmed by serum ceruloplasmin and liver, kidney and heart mineral measurements. CuD rats had lower body weights (BW), hematocrits (Hct), dry kidney weight and total body water (by bioelectrical impedance analysis) than CuS rats. They also had higher heart weights, (HW), HW/BW ratios, % heart water, serum cholesterol, total kidney weight (TKW)/BW ratio, % kidney water, serum Cl, and % body water. CuD rats had higher activities of renal microvillar angiotensin converting enzyme (ACE) and endopeptidase (EP) and lower activities of alkaline phosphatase (AP) and gamma glutamyl transferase (GGT) than CuS rats. DMSO attenuated effects of Cu deficiency on HW, HW/BW, % heart water and Hct. Though DMSO showed some independent effects on renal function, there was no interaction with Cu on TKW/BW, % kidney water, serum Cl or body water. DMSO independently increased ACE and AMP activity, independently decreased AP activity, significantly inhibited the effect of Cu deficiency on GGT activity and had no effect on EP activity. Inhibition of cardiovascular but not renal effects of Cu dificiency by DMSO suggests that there is a difference in the way Cu deficiency affects the metabolism of the two organ systems.

The effect of copper deficiency on rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity

The effect of copper deficiency on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme regulating cholesterol biosynthesis, was investigated in the rat. Male weanling rats were fed semipurified diets containing adequate, marginal, or deficient levels of copper for 6 weeks. Two separate studies were conducted; in the first study, animals were fasted 12 hours prior to analysis and in the second study, animals were fed diets ad libitum. Plasma lipid levels, hepatic cholesterol concentrations, and 3-hydroxy-3-methylglutaryl coenzyme A reductase specific activity, total and active, were determined. Consistent with previous findings, plasma total cholesterol and triglyceride levels were significantly elevated in copper-deficient rats. Copper deficiency resulted in a significant decrease in hepatic total cholesterol levels. Total and active levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase in fed animals were elevated twofold with copper deficiency, with the active form of the enzyme constituting approximately 30% of total activity. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in copper-deficient fasted rats was twofold higher than for the fasted adequate animal; however, fasting did result in a 10-fold reduction in hepatic reductase specific activity. These data support the hypothesis that copper deficiency results in a hypercholesterolemic state in the rat associated with increased hepatic cholesterol synthesis.

Effect of nutritional copper deficiency on carrageenin edema in the rat

The effects of nutritional copper deficiency on carrageenin edema in the rat were investigated with emphasis on studying the correlation between the degree of copper deficiency and the degree of edema. Carrageenin paw edema in both copper-sufficient and copper-deficient groups of rats was compared after either 20, 40, or 60 d on respective diets. The degree of copper deficiency was quantitated by analyzing total copper concentrations in a number of tissues. Other copper dependent parameters were also determined. Results indicated that: (1) although copper sufficient rats showed relatively little change in the degree of edema, copper-deficient rats showed a steady and significant increase in edema from d 20 to 40 to 60; (2) paw edema in copper-deficient animals was highly and negatively correlated to the concentrations of copper in the liver; the correlation with liver Cu,Zn-superoxide dismutase activity, however, was inconsistent; (3) paw edema was not correlated either to copper concentration in tissues other than liver or to plasma ceruloplasmin activity; and (4) aggravation of carrageenin edema in copper-deficient animals seemed to be mediated via an as yet unknown secondary effect of copper deficiency.

The effects of copper deficiency on the pyridinium crosslinks of mature collagen in the rat skeleton and cardiovascular system.

The 3-hydroxypyridinium crosslinks of collagen were quantified in tissues of the skeleton and cardiovascular system of normal and copper-deficient rats. The copper-deficient rats used in this study displayed retarded growth, cardiac hypertrophy, anemia, and lowered liver copper concentrations. Quantification of the crosslinks by high performance liquid chromatography indicated that there were lower concentrations of collagen crosslinks in the hearts of copper-deficient animals, a finding that was manifest in both right and left ventricles. This was in contrast to the collagen of the aorta where no alteration in crosslink concentration was observed. The femoral diaphysis of copper-deficient rats also had lower amounts of collagen crosslinks than copper-supplemented animals, whereas crosslinking in the tibial diaphysis and articular cartilage was relatively unaffected by copper deficiency. These results are discussed with reference to the cardiac and skeletal abnormalities that occur in copper-deficient animals.

Effects of copper deficiency on hepatic and cardiac antioxidant enzyme activities in lactose- and sucrose-fed rats

1. A number of dietary sugars are known to mediate the effects of copper deficiency. The effects of lactose (compared with sucrose) and a dietary Cu deficiency on hepatic and cardiac antioxidant enzyme activities and tissue mineral element status were investigated in the rat. 2. Groups (n 6) of male weanling Wistar rats were provided ad lib. with deionized water and diets containing sucrose (580 g/kg) or sucrose and lactose (387 g/kg and 193 g/kg respectively) with either control (12.0 mg/kg) or deficient (1.5 mg/kg) quantities of Cu for 77 d. 3. Animals consuming the low-Cu diets exhibited significantly decreased tissue Cu levels (P less than 0.01), hepatic and cardiac cytochrome c oxidase (EC 1.9.3.1, CCO) activities (P less than 0.01 and P less than 0.001 respectively) and hepatic Cu-zinc superoxide dismutase (EC 1.15.1.1, CuZnSOD) activity (P less than 0.05). The low-Cu diets also significantly decreased cardiac manganese superoxide dismutase (EC 1.15.1.1, MnSOD), catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities (P less than 0.01, P less than 0.05 and P less than 0.001 respectively). 4. Hepatic Mn was significantly increased in both lactose-fed (P less than 0.001) and Cu-deficient (P less than 0.01) animals. These increases were unrelated to hepatic MnSOD activity. Cardiac Zn was significantly (P less than 0.01) increased in Cu-deficient animals. 5. Lactose feeding resulted in significantly increased cardiac CCO activity (P less than 0.001) but significantly decreased hepatic CuZnSOD (P less than 0.05), catalase (P less than 0.01) and GSH-Px (P less than 0.001) activities. 6. The activities of lactose dehydrogenase (EC 1.1.1.27, LDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PDH) were found to be significantly (P less than 0.05 and P less than 0.01 respectively) increased in Cu-deficient animals and G6PDH activity was significantly (P less than 0.01) decreased as a result of lactose consumption. 7. The observed changes in antioxidant enzyme activities associated with both Cu deficieny and lactose consumption may have important implications for the development of free radical mediated cell damage. However, no significant differences in either hepatic or cardiac levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation, were found.