Copper-zinc Superoxide Dismutase Activity Research Articles

Trace Element Concentrations and Superoxide Dismutase and Catalase Activities in Benign and Malignant Larynx Tumors

The plasma and erythrocyte levels of zinc, copper, and magnesium and the activities of red-cell copper-zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) were determined in patients with benign and malignant tumors of the larynx. Blood samples from patients and healthy controls were drawn using heparinized tubes. The erythrocyte Cu/Zn-SOD and CAT activities were determined spectrophotometrically and the zinc, copper, and magnesium concentrations were determined in erythrocyte and plasma by atomic absorption spectrometry. Variance analysis was employed in the statistical evaluation of the findings. There was a significant increase in red-cell Cu/Zn-SOD activity in the subjects with malignant and benign tumors compared to controls (p<0.001). The CAT activity increased only in the benign tumor group (p<0.01). The plasma zinc concentrations were significantly lower in the malignant tumor group (p<0.05) and significantly higher in the benign tumor group (p<0.01). The erythrocyte copper concentrations were significantly lower in both benign and malignant tumor groups (p<0.001). The plasma copper and magnesium and the erythrocyte magnesium concentrations did not show significant differences relative to controls (p>0.05). The increases in the activities of SOD and CAT activities and the changes in trace elements concentrations can indicate the presence of increased reactive oxygen species that might play a part in the pathogenesis larynx tumors.

Iron supplementation in experimental hyperthyroidism: effects on oxidative stress in skeletal muscle tissue.

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.

Kinetics of wound-induced activation of antioxidative enzymes in Oryza sativa: differential activation at different growth stages

Superoxide dismutase, peroxidase and catalase are major antioxidative enzymes that contribute to the oxidative stress response in plants. The activity of these enzymes was measured in wound-stressed rice plants that were wounded at seedling stage, maximum tillering stage or flowering stage. Kinetics of enzyme activity were examined in leaf extracts post-wounding. Superoxide dismutase activity increased rapidly until 6 h after wounding and was maintained at a high level throughout development. Wound stress-induced changes in manganese superoxide dismutase and copper–zinc superoxide dismutase activities were detected using a native activity gel. In contrast, catalase was rapidly deactivated and peroxidase was transiently activated and then deactivated after wounding. However, high peroxidase activity was maintained at maximum tillering stage of development. These observations suggest that rice antioxidant enzymes are differentially activated by wound stress depending on the plant growth stage, and that the antioxidative enzymes are activated by wounding in two phases. The first phase involves activation of superoxide dismutase and peroxidase and rapid deactivation of catalase. The second phase involves deactivation of peroxidase under conditions of severe stress. Deactivation of peroxidase and catalase may lead to accumulation of hydrogen peroxide, which can activate of a series of additional defense mechanisms.

Differential expression of the lenticular antioxidant system in laboratory animals: A determinant of species predilection to oxidative stress-induced ocular toxicity?

Purpose. Various animal species have been used to study oxidative stress-induced cataractogenesis; however, given that differences in the expression of the lens antioxidant system may influence species susceptibility to oxidative stress, we compared and contrasted a broad spectrum of components of the lens antioxidant system in dog, rat, marmoset, and rabbit. Methods. Lenses collected from beagle dogs, Sprague-Dawley rats, marmosets, and New Zealand white rabbits were assayed for reduced glutathione (GSH), and activities of copper-zinc and manganese superoxide dismutase (CuZn-SOD; Mn-SOD), catalase (CAT), glutathione peroxidase (GPX), ?-Glutamylcysteine synthetase (GCS), glutathione reductase (GR), glutathione-S-transferases (GST), and glucose-6-phosphate dehydrogenase (GPDH), and Trolox equivalent antioxidant capacity (TEAC). Results. Expression of the lens antioxidant system varied considerably between species. Marmoset lens contained the highest levels of GSH, its respective biosynthetic and recycling enzymes GCS and GR, and the associated H2O2-dismutation enzyme GPX. Activities of both SOD isoforms were also highest in marmoset lens. However, activities of the xenobiotic-conjugating enzyme GST and NADPHgenerating enzyme GPDH were relatively low. In contrast, dog lens had the lowest levels of GSH, GCS, GR, and Cu-Zn SOD (1/2, 1/2 and 1/33, and 1/63 that in marmoset) but highest levels of GST and GPDH. Rabbit lens contained the highest CAT activity, at up to 3.5-fold that for marmoset and rat. Conclusions. These results demonstrate substantial variation in lens antioxidant systems between different laboratory animal species. Given that such variation may affect relative susceptibility to oxidative stress-mediated ocular toxicity, our findings may provide useful information when choosing different animal species for lens research.

Thyroxine and tri-iodothyronine differently affect uncoupling protein-1 content and antioxidant enzyme activities in rat interscapular brown adipose tissue.

The activity of the antioxidant enzymes copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity, uncoupling protein-1 (UCP1) content, catecholamine degrading enzyme monoamine oxidase (MAO) activity and malonyl dialdehyde (MDA) concentration were studied in rat interscapular brown adipose tIssue (IBAT). Rats were treated with either thyroxine (T4) or tri-iodothyronine (T3) for five days and then exposed to cold (4 degrees C, 24 h) or housed at room temperature (22 degrees C). Under basal conditions, T3 treatment significantly increased UCP1 content and MnSOD activity whereas CuZnSOD, CAT and MAO activities were significantly decreased. Thyroxine treatment significantly decreased IBAT CAT activity while MDA levels markedly increased. Cold exposure induced a significant augmentation of UCP1 content and MnSOD and mGPDH activities only in animals that were rendered hyperthyroid by T4 treatment. In T3-treated animals acutely exposed to cold stress, MDA concentration, an indicator of lipid peroxidation, was significantly higher compared with that of T3-treated animals housed at room temperature. However, in T4-treated animals, MDA concentrations were markedly lower. These results show that T4 and T3 differently affect IBAT parameters studied not only under basal but also under cold-stimulated conditions.

Increased oxidative stress and hypozincemia in male obesity

Objectives Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals. Design and methods Seventy-six obese men (body mass index (BMI) > 30 kg/m 2) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured. Results We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group ( p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls ( p = 0.001) whereas erythrocyte TBARS levels were significantly higher ( p = 0.001) than those of the control group. Conclusion We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain

Typical and atypical antipsychotics significantly differ in their neurotransmitter receptor affinity profiles, and their efficacy and side effects in schizophrenic patients. Typical antipsychotics have been found to increase the oxidative (i.e. free radical-mediated) cellular injury in rats. Since schizophrenia also involves oxidative injury, the understanding of differential effects of these antipsychotics on expression of antioxidant enzymes and oxidative injury may be very critical. The effect of chronic exposure of haloperidol (HAL), a typical antipsychotic, was compared to effects of risperidone (RIS) or clozapine (CLZ) or olanzapine (OLZ), atypical antipsychotics on antioxidant defense enzymes and lipid peroxidation in the rat brain. The levels of antioxidant enzymes and hydroxyalkenals (HAEs) were measured in rat brain cytosol and fatty acids were measured in brain cell membranes. Chronic HAL treatment for both 45 and 90 days significantly decreased manganese-superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT) activity with parallel marked increase in (HAEs), a marker of lipid peroxidation in rat brain. The levels of enzymatic activity very well correlated with the levels of enzyme proteins indicating that the changes were probably in the expression of net protein. However, RIS, CLZ and OLZ treatments did not produce any alterations in the levels of antioxidant enzymes and HAEs, both after 45 and 90 days. There were no alterations in the levels of saturated as well as polyunsaturated fatty acids in brain membranes. These findings indicate that chronic administration of HAL, but none of the studied atypicals induce oxidative stress by persistent changes in the levels of antioxidant enzymes and cause membrane lipid peroxidation.

Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotectic enzymes in humans.

Obesity, defined as a body mass index (BMI) greater than 30 kg/m(2), is now recognised as a risk factor for diabetes mellitus, hyperlipidaemia, colon cancer, sudden death and other cardiovascular diseases. In this study, it is hypothesized that obesity is an independent risk factor for lipid peroxidation and decreased activities of cytoprotective enzymes in humans. Fifty normal healthy subjects with healthy BMI (19-25 kg/m(2)) and 250 subjects with different grades of obesity (30-50 kg/m(2)) with no history of smoking or biochemical evidence of diabetes mellitus, hypertension, hyperlipidaemia, renal or liver disease or cancer. To test this hypothesis, we assessed lipid peroxidation and cytoprotection by measuring the concentrations of plasma malondialdehyde (P-MDA) and the activities of erythrocyte copper zinc-superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GPX). The concentration of P-MDA was significantly lower (P<0.001) in subjects with healthy BMI (2.53+/-0.04 micro mol/l) than in those with BMI above 40 kg/m(2) (4.75+0.05 micro mol/l). Furthermore, there was a significantly positive association (r=0.342, P=0.013) between BMI and P-MDA. On the other hand, subjects with healthy BMI had significantly higher (P<0.001) erythrocyte CUZn-SOD (1464+/-23 units/g Hb) and GPX (98.4+/-3.3 units/g Hb) than those with BMI above 40 kg/m(2) (1005+/-26 units/g Hb) and (84.3+/-6.7 units/g Hb) respectively. Furthermore, erythrocyte CuZn-SOD and GPX activities were negatively associated with BMI (r=-0.566, P=0.005 and r=-0.436, P=0.018) respectively. It is concluded from these results that obesity in the absence of smoking, diabetes mellitus, hyperlipidaemia, renal or liver disease causes lipid peroxidation and decreased activities of cytoprotective enzymes, and should therefore receive the same attention as obesity with complications.

Impact of different combined preservation modalities on warm ischemic kidneys: effect on oxidative stress, hydrostatic perfusion characteristics and tissue damage.

Hemodynamic disorders in brain dead organ donors induce hypoxia, warm ischemia and finally tissue damage. A cold preservation period also induces tissue and cellular lesions. The two major modes of preservation are cold storage (CS) and hypothermic pulsatile perfusion (HPP). We aimed to compare the influence of each mode of preservation and their combination on oxidative stress, perfusion characteristics and tissue damage, after a period of warm ischemia. Rat kidneys which had undergone ischemia (0, 30, 60 min) were preserved either by CS (12, 24 h), or by HPP (12 h), or by a combination of both (HPP+CS, CS+HPP), in University of Wisconsin cold storage solution (UWCSS) at + 4 degrees C. During HPP, renal vascular pressure decreased then increased to reach 90 mmHg after perfusion for 7 h. If HPP followed CS, the mean pressure reached 200 mmHg, showing successive high amplitude peaks. HPP had a deleterious effects on tissue structure with tubular necrosis, and induced an increase in catalase (Cat) and a decrease in manganese superoxide dismutase (Mn SOD) and gluthatione peroxidase (GPx) activity. Copper zinc superoxide dismutase (Cu/Zn SOD) activity was not reduced except with CS+HPP. During CS, we observed an increase in GPx, Cu/Zn SOD and Cat activity, a decrease in Mn SOD activity and no histological alterations in the kidney. CS induces a slight oxidative stress which is not important enough to induce major tissue damage. HPP with UWCSS induces a stronger stress, which overpowers the antioxidant defences, inducing tissue damage. The reperfusion of HPP with UWCSS emphasises the stress initiated by CS. In addition an increase in damage occurred in the CS + HPP group.

Early changes in myocardial antioxidant enzymes in rats treated with adriamycin.

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.

Evidence of oxidative stress following the viral infection of two lepidopteran insect cell lines

The infection of Spodoptera frugiperda Sf-9 (Sf-9) and Trichoplusia ni BTI-Tn-5B1-4 (Tn-5B1-4) insect cell lines with Autographa californica multiple nucleopolyhedrovirus (AcMNPV) resulted in increased levels of lipid hydroperoxides and protein carbonyls. In addition, the viral infection resulted in a significant decrease in the reduced glutathione to oxidized glutathione (2GSH/GSSG) ratio. These results are all consistent with an increased level of oxidative stress as a result of the viral infection. It was also observed that the oxidative damage corresponded to reduced cell viability, i.e., the results are consistent with the premise that oxidative damage contributes to cell death. Finally, the measured intracellular activities of most of the antioxidant enzymes, specifically manganese superoxide dismutase (MnSOD), ascorbate peroxidase (APOX), and catalase (CAT, not present in Sf-9 cells), did not significantly decrease following viral infection. In contrast, the measured activity of copper-zinc superoxide dismutase (CuZnSOD) decreased in the Sf-9 and Tn-5B1-4 cells following AcMNPV infection.

Effects of tobacco smoking on plasma selenium, zinc, copper and iron concentrations and related antioxidative enzyme activities

Objectives: The aim of the study was to investigate whether alterations in antioxidative enzyme activities are dependent on their cofactor concentrations in tobacco smokers. Design and methods: Plasma selenium, copper, zinc and iron concentrations, and the activities of related erythrocyte antioxidative enzymes copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tobacco smokers and compared with those of nonsmokers. Plasma thiocyanate levels were measured as an index of smoking status. Results: While plasma copper concentration and erythrocyte Cu-Zn SOD activity were significantly higher, plasma selenium concentration and erythrocyte GSH-Px activities were significantly lower in tobacco smokers than in nonsmokers. There was no significant difference in plasma iron and zinc concentrations or erythrocyte CAT activity between the two groups. There were significant positive correlations between erythrocyte GSH-Px and plasma selenium levels, between Cu-Zn SOD and copper levels, and between CAT and iron levels, and a negative correlation between plasma thiocyanate and selenium content in tobacco smokers. Conclusions: These findings suggest that antioxidative enzyme activities change depending on their cofactor concentrations in tobacco smokers.

Copper Transport and Metabolism Are Normal in Aceruloplasminemic Mice

Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of the copper found in the plasma of vertebrate species. Although this protein is known to function as an essential ferroxidase, the role of ceruloplasmin in copper transport and metabolism remains unclear. To elucidate the role of ceruloplasmin in copper metabolism, the kinetics of copper absorption, transport, distribution, and excretion were examined utilizing (64)Cu in wild-type and aceruloplasminemic mice. No differences in gastrointestinal absorption, hepatic uptake, or biliary excretion were observed in these animals. Furthermore, steady state measurements of tissue copper content utilizing (64)Cu and atomic absorption spectroscopy revealed no differences in the copper content of the brain, heart, spleen, and kidney. Consistent with these findings, the activity of copper-zinc superoxide dismutase in these tissues was equivalent in wild-type and ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in aceruloplasminemic mice because of the loss of ferroxidase function. Hepatic copper content was markedly increased in aceruloplasminemic mice. As no differences were observed in copper absorption or biliary copper excretion, these data suggest that in these animals, hepatocyte copper intended for ceruloplasmin incorporation is trafficked into a compartment that is less available for biliary copper excretion. Taken together, these data reveal no essential role for ceruloplasmin in copper metabolism and suggest a previously unappreciated complexity to the subcellular distribution of this metal within the hepatocyte secretory pathway.

Effect of sulfur dioxide inhalation on erythrocyte antioxidant status, food intake, and lipid peroxidation during aging.

The effect of sulfur dioxide on red blood cell antioxidant status and lipid peroxidation was investigated in young (3 mo), middle-age (12 mo), and old (24 mo) male albino rats. Ten ppm of sulfur dioxide was administered to the rats in the sulfur dioxide groups in an exposure chamber. Exposure occurred 1 hr/d, 7 d/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. Copper-zinc superoxide dismutase, glutathione peroxidase, catalase, glutathione, and glutathione-S-transferase activities were significantly decreased in the middle-aged and older groups, compared with the young group. Sulfur dioxide exposure significantly decreased copper-zinc superoxide dismutase activity in all experimental groups, compared with controls. Sulfur dioxide exposure significantly increased enzyme and glutathione activities.

Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol.

The clinical usefulness of adriamycin is restricted by the development of congestive heart failure. It has been suggested that probucol, a strong antioxidant, completely prevents adriamycin-induced cardiomyopathy without interfering with its antitumor properties. The present study investigated the effects of adriamycin and probucol on myocardial antioxidant enzyme activities and immunoreactive protein levels in rats. Activities and protein levels of glutathione peroxidase (GSHPx) were significantly decreased from 2 to 24 hours, and those of manganese superoxide dismutase were decreased at 1 and 2 hours after adriamycin treatment. These changes were prevented by probucol. Catalase activity was increased from 2 to 24 hours after adriamycin treatment, but its protein levels were not significantly changed. Copper zinc superoxide dismutase activity and protein level were not changed at any time. Myocardial lipid peroxidation was found to be significantly higher at all time points, and this change was also prevented by probucol. Treatment with probucol alone increased GSHPx activity at 2 weeks, and in these hearts, lipid peroxidation was lower than the control value. Within 24 hours, there was no mortality in any of the groups. It is suggested that an early and persistent decrease in GSHPx activity and protein may play an important role in the pathogenesis of adriamycin-induced cardiomyopathy, worsening heart failure and mortality.

Defective antioxidant defense system in patients with a human leptin gene mutation.

Antioxidant defense system prevents the organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Changes in the antioxidant defense mechanisms and alterations of several essential trace elements in both plasma and various tissues of ob/ob mice have been reported previously. Recent finding of the restoration of the defective antioxidant enzyme activity after leptin treatment in ob/ob mice suggests a putative role of leptin in modulation of antioxidant enzyme activity. Therefore, the aim of this study was to investigate whether antioxidant enzymes and trace elements could also be altered in patients with leptin gene mutation. Seven patients (five men and two women, two of them are homozygous and 5 are heterozygous) with leptin gene mutation and 31 healthy, sex- and age-matched and non-related to the patients (24 male and 9 female), control volunteers were enrolled in the study. Plasma and erythrocyte glutathione peroxidase (GSH-Px) and erythrocyte copper-zinc superoxide dismutase (CuZn-SOD) activities were measured spectrophotometrically. Plasma selenium (Se), manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) levels were measured by atomic absorption spectrophotometry. Mean Cu and Fe levels in patients were not significantly different than those in controls whereas mean Se, Zn and Mn levels were significantly lower in patients than those of controls (P=0.007, P=0.001, and P=0.001, respectively). Erythrocyte GSH-Px (39%), plasma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were significantly lower than those of the control group (P=0.001, P=0.002, P=0.001, respectively). In conclusion, our results demonstrate that the activity of antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreased in both homozygous and heterozygous subjects with leptin gene mutation. We suggest that both leptin and trace elements might be involved in the modulation of antioxidant defense system.

Identification of the copper-zinc superoxide dismutase activity in Mycoplasma hyopneumoniae

Copper-zinc superoxide dismutase (Cu/ZnSOD), a key enzyme in defense against toxic oxygen-free radicals, is widespread in eukaryotes and several species of gram-negative bacteria. The presence of this enzyme in Mycoplasma hyopneumoniae ( M. hyopneumoniae), the primary pathogen of mycoplasmal pneumonia in pigs, was examined since the polyclonal antibody against bovine Cu/ZnSOD was dominantly cross-reactive with the M. hyopneumoniae Cu/ZnSOD from whole cellular proteins. In situ activity staining on SDS-PAGE showed that the molecular mass of M. hyopneumoniae Cu/ZnSOD in reducing form was ≈17 kDa. The presence of Cu and Zn ions at the active site of the enzyme was confirmed on the basis of inhibition by KCN and by H 2O 2. The activity of M. hyopneumoniae Cu/ZnSOD on both SDS- and native-polyacrylamide gels was completely inhibited by 2 mM KCN and the gels showed no iron-containing SOD (FeSOD) or manganese-containing SOD (MnSOD) in the crude extracts. The activity of M. hyopneumoniae Cu/ZnSOD in crude extract was 70 units/mg protein and was 55% inhibited by 5 mM KCN and 56% inactivated by 40 mM H 2O 2. This enzyme was growth-stage dependent and evidenced markedly higher production during the early log phase. Different expression levels of Cu/ZnSOD activity in field isolates were also detected. Taken together, the presence of Cu/ZnSOD in M. hyopneumoniae was identified for the first time.

Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias

Free radicals are highly reactive species that have been implicated in the pathogenesis of many diseases. Reactive oxygen species can initiate lipid peroxidation and DNA damage leading to mutagenesis, carcinogenesis and cell death, if the antioxidant system is impaired. This study was undertaken to examine the prevalence of oxidative stress and the role of antioxidant defence in untreated leukemia patients. The generation of superoxide anion and hydrogen peroxide by leukocytes, plasma malondialdehyde levels, red cell copper zinc superoxide dismutase (Cu–Zn SOD) and glutathione peroxidase (GSH-PX) activities were determined in 30 patients with different types of leukemias prior to therapy. The superoxide anion generation by polymorphonuclear leukocytes was found to be significantly increased in leukemia patients especially those with acute lymphocytic and nonlymphocytic leukemias, while the hydrogen peroxide levels were comparable to the control values. Plasma lipid peroxidation products in untreated leukemia patients were in the normal range. Red cell Cu–Zn SOD and GSH-PX activities were significantly increased and showed no correlation with the hemoglobin content. Although superoxide generation was high, lipid peroxide levels were normal in these patients. This might be due to the increased activities of the antioxidant enzymes (SOD, GSH-PX) which counteract lipid peroxidation. Increased free radical generation, especially superoxide anion in leukemia patients and increased antioxidant defence enzymes, which is an adaptive protective response, are indicative of mild oxidative stress. There were no significant differences for the parameters cited above between different types of leukemias, suggesting that the changes are not specific to the type of leukemia.

Antioxidant enzyme activities and trace element concentrations in ischemia-reperfusion.

In this study, we investigated the impact of ischemia-reperfusion on antioxidant enzyme activities and trace element concentrations. For this purpose, ischemia was initiated by clamping superior mesenteric artery of Wistar (albino) rats for 30 min, followed by reperfusion for 20 min. Immediately after reperfusion, blood samples were taken and examined for red cell copper-zinc superoxide dismutase (Cu-Zn-SOD), catalase (CAT), and glutathione peroxidase (GPx) activities spectrophotometrically and plasma zinc, copper, and magnesium concentrations by atomic absorption spectrophotometer. In the ischemia-reperfusion group, red cell Cu-Zn-SOD activity and plasma zinc and copper concentrations were increased significantly (p < 0.001) when compared to the control group; however, the increases in GPx activity and plasma magnesium concentration were not significant (p > 0.05). We also found a significant (p < 0.01) decrease in catalase activity. Free radicals released as a consequence of ischemia-reperfusion caused significant alterations in antioxidant enzymes and in the concentrations of trace elements.

Altered Copper Status in Adult Men with Cystic Fibrosis

Objectives: To measure indices of copper status in adult men with cystic fibrosis (CF). A previous study in children showed changes in copper homeostasis compared to controls. This study was designed to investigate whether this observation persisted into adulthood.Methods: This was a case-control age-matched study using seven men with CF and six healthy men. Blood samples were drawn into metal free tubes and fractionated into plasma, polymorphonuclear cells, mononuclear cells and erythrocytes. Cell fractions were assayed for copper and CuZn-superoxide dismutase; plasma was assayed for ceruloplasmin.Results: The men with cystic fibrosis had significantly greater plasma copper and ceruloplasmin activity, yet had significantly lower copper-zinc superoxide dismutase activity in mononuclear and polymorphonuclear cells. Furthermore, the mononuclear cells of the cystic fibrosis subjects had about 45% percent less copper-zinc superoxide dismutase protein. Cellular copper levels were not statistically different between the two groups. A significant correlation was found between lung function and copper-zinc superoxide dismutase activity in the polymorphonuclear cells. Iron status was normal.Conclusions: The results indicate that individuals with cystic fibrosis have altered copper distribution compared to control individuals. Some aspects are characteristic of an inflammatory response; however, other measures suggest that copper homeostasis may be abnormal. It is not known whether the deviation in copper homeostasis in these individuals is a result of poor copper absorption, inadequate dietary intake, a result of their chronic inflammation or a direct effect due to the defect in ion transport caused by the disease. However, this research suggests that the severity of the disease and the activity of a copper dependent enzyme may be related. Further work will be necessary to determine the cause of the abnormal copper homeostasis and whether correcting it has any bearing on the course of the disease.