The relation between selenium, zinc and copper concentration and the trace element dependent antioxidative status.

An imbalance in the antioxidative system was connected with the development of a number of pathological processes. In order to receive values of a healthy group and to evaluate pathological changes of the trace element dependent antioxidative status in future, we investigated 99 healthy volunteers (45 male and 54 female, mean age 37.4 +/- 11.7 years). We determined the concentrations of Se, Cu and Zn, the concentrations of malondialdehyde (MDA) and the activities of the Se dependent glutathione peroxidase (GSH-Px) and the Zn/Cu dependent superoxide dismutase (SOD). The plasma concentrations (mean +/- SD) for Se, Cu and Zn were 0.84 +/- 0.10 micromol/l, 15.6 +/- 2.78 micromol/l and 12.6 +/- 1.80 micromol/l, resp., and for non protein-bound and protein bound MDA 0.27 +/- 0.07 micromol/l and 1.11 +/- 0.25 micromol/l, resp. The activity of GSH-Px in plasma and erythrocytes was 130 +/- 20.8 U/l and 19.8 +/- 4.18 U/mg Hb, resp. and of SOD in erythrocytes 3,159 +/- 847.2 U/g Hb. In plasma positive correlations have been found between Se concentrations and GSH-Px activities (p < 0.002, r = 0.31) and between GSH-Px activities and concentrations of non protein-bound MDA (p = 0.004, r = 0.28). A negative correlation has been observed between GSH-Px activities in plasma and in erythrocytes. The higher the concentrations of Cu in erythrocytes, the higher were the activities of SOD (p = 0.03, r = 0.22) and GSH-Px in erythrocytes (r = 0.26, p = 0.01), while an increasing activity of GSH-Px in these cells correlated with a decreasing concentration of non protein-bound MDA (r = -0,31, p = 0.002). An increase in BMI was connected with an increase in protein-bound MDA and a decrease in GSH-Px activities in pLasma (p = 0.002 and r = 0.23). As the results demonstrate, Se and Cu concentrations in erythrocytes can improve the trace element dependent antioxidative status.     

Plasma and erythrocytes antioxidant status and trace element levels in proteinuric patients with moderate glomerular function.

The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes.     

Alterations of serum selenium, zinc, copper, and iron concentrations and some related antioxidant enzyme activities in patients with cutaneous leishmaniasis

The aim of this study was to measure the alterations in serum selenium (Se), copper (Cu), zinc (Zn), and iron (Fe) concentrations and their carrier proteins, ceruloplasmin (Cp), transferrin (Tf) albumin, and related antioxidant enzyme activities, erythrocyte Cu-Zn Superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in patients with cutaneous leishmaniasis (CL). Erythrocyte Cu-Zn SOD activities, serum Cu concentrations, and Cp levels were found to be significantly higher in the patients group than those of controls. However, GSH-Px and CAT activities and Se, Zn, Fe, and Tf levels were lower in patients than in the control subjects. There were positive important correlation’s between Cu-Zn SOD and Cp, Cu-Zn SOD and Cu, Cp and Cu, GSH-Px and Se, and Fe and CAT in the patients group. Our results showed that serum essential trace elements Se, Zn, Cu, and Fe concentrations and their related enzymes Cu-Zn SOD, GSH-Px, and CAT activities change in CL patients. The changes may be a part of defense strategies of organism and are induced by the hormonelike substances.     

Trace mineral status in post menopausal women: impact of hormonal replacement therapy.

The risks of disturbances in trace mineral nutrition and metabolism are high following menopause. The aim of the study was to investigate the trace mineral status in postmenopausal women and the influence of hormonal replacement therapy on this status. Forty-four healthy postmenopausal women, aged 50-60 years old participated in the study. Eighteen were treated by combined hormonal replacement therapy (HRT) per os for at least two years, and 26 were untreated. Plasma trace mineral levels (Zn, Se, Cr, Mn, Cu), red blood cell antioxidant enzymes (Cu-Zn SOD, Se-GPX, Cu), urinary Zn, Cr, Mg, and Ca excretion were measured. Zinc, selenium and manganese plasma levels, activities of Cu-Zn-SOD and GSH-Px in erythrocytes were not statistically different between the two groups. The percentage of zinc plasma levels below the cut off of 10.7 micromol/L was higher in HRT treated group than in untreated one, whereas zinc excretion was reduced. Plasma copper concentrations were higher in women treated by HRT, whereas erythrocyte copper levels were not modified. Plasma chromium concentrations were significantly higher in women receiving HRT and urinary Cr excretion was decreased. The HRT group also exhibited lower losses of urinary zinc and magnesium than untreated women. These data suggest that hormonal replacement therapy provides beneficial effects on trace mineral status related to menopause.     

Estimation of minimum alveolar concentration (MAC) for halothane, enflurane and isoflurane in spontaneously breathing guinea pigs

MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents.     

Elevated ornithine decarboxylase activity in the rat liver following exposure to halothane,enflurane and isoflurane

Exposure of rats to the volatile anesthetics, halothane, enflurane and isoflurane and low FIO₂ (0.8%) for two hours results in a transient induction of ODC appearing maximally four hours after exposure. Without the low oxygen accompanying the anesthetic or the low oxygen alone, no significant induction of ODC occurred. The concentration of anesthetic used to produce the ODC induction were 0.5% halothane, 1.5% enflurane and 1.4% isoflurane. Except for halothane, reducing the anesthetic concentration only slightly reduced the effect on ODC levels to control values. Reduction of halothane concentrations to 0.1% was required to reduce the values to control levels. Pretreatment of the animals with either cycloheximide or actinomycin D delayed the onset of ODC induction. The data support the fact that liver damage can occur in the absence of metabolism of the drug.     

Carbon monoxide production from five volatile anesthetics in dry sodalime in a patient model: halothane and sevoflurane do produce carbon monoxide; temperature is a poor predictor of carbon monoxide production

BACKGROUND: Desflurane and enflurane have been reported to produce substantial amounts of carbon monoxide (CO) in desiccated sodalime. Isoflurane is said to produce less CO and sevoflurane and halothane should produce no CO at all.The purpose of this study is to measure the maximum amounts of CO production for all modern volatile anesthetics, with completely dry sodalime. We also tried to establish a relationship between CO production and temperature increase inside the sodalime. METHODS: A patient model was simulated using a circle anesthesia system connected to an artificial lung. Completely desiccated sodalime (950 grams) was used in this system. A low flow anesthesia (500 ml/min) was maintained using nitrous oxide with desflurane, enflurane, isoflurane, halothane or sevoflurane. For immediate quantification of CO production a portable gas chromatograph was used. Temperature was measured within the sodalime container. RESULTS: Peak concentrations of CO were very high with desflurane and enflurane (14262 and 10654 ppm respectively). It was lower with isoflurane (2512 ppm). We also measured small concentrations of CO for sevoflurane and halothane. No significant temperature increases were detected with high CO productions. CONCLUSION: All modern volatile anesthetics produce CO in desiccated sodalime. Sodalime temperature increase is a poor predictor of CO production.     

Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation

Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.     

Dantrolene protects erythrocytes against oxidative stress during whole-body irradiation in rats

In our study, we examined the radioprotective effects of dantrolene against gamma irradiation-induced damage of blood cells after total body irradiation of rats. Rats were divided into three groups of eight rats each. The first group was the control group receiving no dantrolene or irradiation, the second group received total body irradiation (RT) with 5 Gy of gamma irradiation only, and the third group received dantrolene at a dose of 5 mg x kg(-1) plus RT. Dantrolene was given intraperitoneally 30 min before RT. All groups were sacrificed 2 h after RT, and blood samples were taken. Leukocyte, and thrombocyte counts and hemoglobin levels were measured. Furthermore, malondialdehyde (MDA) levels in plasma and erythrocytes and superoxide dismutase (SOD) and glutathione peroxidase activities (GSH-Px) in erythrocytes were determined. It was found that pretreatment with dantrolene at a dose of 5 mg x kg(-1) significantly reduced the MDA levels and increased the antioxidant SOD and GSH-Px activities, and prevented the decrease in leukocyte and thrombocyte counts. We conclude that dantrolene has clear antioxidant properties when given prior to radiation exposure and the protective effect of dantrolene against damage inflicted by radiation, depends, at least in part, on the decrease in lipid peroxidation and increase in the activity of antioxidant enzymes SOD and GSH-Px.     

Lipid peroxidation and antioxidant system in the blood of cancerous patients with metastasis

Free-radical-mediated damages may play an important role during metastasis. To investigate their relevance in the metastatic process MDA levels, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and selenium, zinc and copper contents were determined in plasma and erythrocytes from 20 cancerous patients with metastasis and 30 age-matched controls. Significantly higher concentrations of MDA in plasma as well as in erythrocytes were found comparing to the control group. In both plasma and erythrocytes, GPX activity and selenium and zinc levels were significantly lower in patients than in controls. However, SOD activity in erythrocytes and copper levels in both plasma and erythrocytes were significantly higher in patients. The impaired antioxidant system may favor accumulation of free radicals which may induce the process of metastasis. On the other hand, it is possible that the antioxidant system is impaired as a consequence of abnormality in the antioxidative metabolisms due to the cancer process.     

Nitric oxide levels and antioxidant enzyme activities in jaundices of premature infants

Free radicals are effective in the genesis of several diseases in the neonatal period. This study aimed to show the relationship between serum bilirubin levels and plasma nitric oxide and the activity of enzymes in the erythrocyte such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in premature infants. In the study, 20 premature infants with newborn jaundice were included and the control group was formed by 15 premature infants without jaundice. Venous blood samples were taken from all neonates in the study and control groups on the first day of hospitalization. Plasma nitric oxide levels and activities of SOD, GSH-Px and CAT enzymes in the erythrocytes were investigated in these samples. Plasma nitric oxide and serum bilirubin levels were found to be significantly higher in the study group (47.4 +/- 7.25 micromol l(-1), 18.41 +/- 3.28 mg dl(-1), respectively) than those in the control group (33.46 +/- 6.43 micromol l(-1), 4.35 +/- 0.60 mg dl(-1), respectively; p < 0.001). In addition, erythrocyte SOD, GSH-Px and CAT enzyme activities (724 +/- 78.61, 673 +/- 90.5, 63 +/- 12.8 U g(-1) Hb, respectively) were found to be significantly lower in the study group than those in the control group (1208 +/- 129.04, 1097.6 +/- 75.8, 99.06 +/- 12.4 U g(-1) Hb, respectively, p < 0.001). It was concluded that in the aetiology of hyperbilirubinemia, neonatal erythrocytes and nitric oxide reactions are affected differently and that erythrocyte haemolysis caused as a result of these effects may play a role in the aetiopathogenesis of unconjugated hyperbilirubinemia. Haemolysis may also be seen because of the inadequacy of the protection by erythrocytes against the cytotoxic effects of free radicals resulting from the lack of antioxidant enzymes in these cells.     

Erythrocyte and plasma trace element levels in clinical assessments

On the basis of original investigations on zinc, copper, and selenium levels in plasma and erythrocytes of Down's syndrome (DS), cystic fibrosis (CF), and control subjects, the possible importance of erythrocytic trace element concentrations in clinical analysis is emphasized. Red blood cell levels of copper and zinc were found significantly increased in both groups of diseased patients as compared to age-matched controls, although plasma levels did not statistically differ. Plasma selenium levels were significantly lower in both investigated groups, but red blood cell levels were only decreased in CF and were not different from controls in DS. Significant differences were also found between zinc, copper, and selenium levels in erythrocytes of two control groups originating from distinct geographic areas, although plasma levels were not statistically different. Some factors likely to modify trace element concentrations in erythrocytes are examined and a more systematic determination of these levels is suggested for use in clinical analysis.     

Do Zinc and Selenium Prevent the Antioxidant, Hepatic and Renal System Impairment Caused by Aspirin in Rats?

Aspirin is widely used as an antiinflammatory drug especially in children with rheumatic fever arthritis. The diminishing effects of aspirin on antioxidant enzymes and hepato-renal systems at high doses are well-known. It is now evident that the damage at antioxidant system worsens the clinical picture of the disease and prolongs the treatment time. Thus, we investigated the effect of antioxidant enzyme cofactors-zinc and selenium-supplementation on superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels (erythrocyte and liver) and hepato-renal toxicity during aspirin treatment at therapeutic doses. The rats were divided into five groups. The first and second groups were given aspirin 75 mg/kg/day and aspirin plus selenium (Selenium 200, selenium 200 mg tablet as selenium yeast, GNC) and zinc (Zinc 100, zinc 100 mg tablet as zinc gluconate, GNC), respectively, the third and fourth take 50 mg/kg/day aspirin and aspirin plus selenium and zinc twice a day, respectively. The fifth group was control. The rats were treated with aspirin for 5 weeks as in the treatment of rheumatic fever arthritis in children. Erythrocyte SOD and MDA levels were preserved with supplementation, whereas there was no change for GSH-Px levels. Liver SOD, GSH-Px, and MDA levels were not changed. In zinc- and selenium-supplemented groups, the levels of serum alanine aminotransferase, uric acid, and direct bilirubin levels were found statistically decreased compared with nonsupplemented groups. There was no significant histopathologic change in specimens of hepatic and renal tissues. Trace element supplementation may prevent free radical damage and shorten treatment time in children using long-term aspirin treatment.     

Effects of halothane, enflurane, and isoflurane on measurements of Ca(2+) by calcium electrode and aequorin luminescence

We assessed the possible effects of the volatile halogenated anesthetics halothane, enflurane, and isoflurane on Ca(2+) electrode measurements and on the Ca(2+) sensitivity of the bioluminescent protein aequorin. In Ca(2+)-EGTA buffers of different pCa values (7. 870, 6.726, 6.033, 4.974, 4.038, and 2.995) and in serial Ca(2+) dilutions (10(-4), 10(-3), and 10(-2) M), halothane, enflurane, and isoflurane each caused a concentration-dependent and reversible increase in the absolute value of the negative electrode potential. Isoflurane and enflurane had larger effects than halothane. Neither of these anesthetics changed aequorin luminescence at any pCa tested in the range 2-8. There was no potentiation or inactivation of aequorin luminescence over a period of up to 2 h. These results suggest that (1) halothane, enflurane, and isoflurane interfere with Ca(2+) electrode measurements, most likely by changing the physicochemical properties of the membrane; (2) these anesthetics do not inactivate or otherwise modify the characteristics of the reaction of Ca(2+) with aequorin; and (3) these anesthetics do not change the apparent affinity of EGTA for Ca(2+).     

Cardiopulmonary,hematological, serum biochemical and behavioral effects of sevoflurane compared with isoflurane or halothane in spontaneously ventilating goats

This study compares cardiopulmonary, hematological, serum biochemical and behavioral effects of sevoflurane, isoflurane or halothane anesthesia in spontaneously breathing, conventionally medicated goats. Six male adult goats were anesthetized repeatedly at 2-week intervals with three anesthetics. Goats were administered atropine (0.1 mg/kg) intramuscularly, and 10 min later, induced to anesthesia by an intravenous infusion of thiopental (mean 14.3 mg/kg). After intubation, goats were anesthetized with halothane, isoflurane or sevoflurane in oxygen and maintained at surgical depth of anesthesia for 3 h. Recovery from anesthesia with sevoflurane was more rapid than that with isoflurane or halothane. Time-related hypercapnia and acidosis were observed during halothane anesthesia, but not observed during sevoflurane or isoflurane anesthesia. Both hypercapnia and acidosis during sevoflurane anesthesia did not differ from isoflurane anesthesia, but were less during halothane anesthesia, especially at prolonged maintenance period. There were no significant differences between anesthetics in respiration and heart rates, arterial pressures, hematological and serum biochemical values. It was concluded that sevoflurane is an effective inhalant for use in goats showing the most rapid recovery from anesthesia, and that cardiopulmonary effects of sevoflurane are similar to isoflurane than halothane.     

Comparison of the effects of volatile anesthetics in varying concentrations on brain energy metabolism with brain ischemia in rats

The effects of varying concentrations and types of volatile anesthetics on neurochemical sequelae of brain ischemia were evaluated in the rat. Rats were assigned to treatment defined by a 3×3 design (anesthetic type and dose) with 5 rats/cell. Each group received halothane, enflurane, or isoflurane 0.5, 1.0, or 2.0 MAC (minimal alevolar concentration). This was followed by preischemic plasma glucose sampling, 5 min hypotension (30 mmHg) and 5 min decapitation cerebral ischemia. Preischemia plasma glucose increased with increasing anesthetic concentration and was highest in the isoflurane groups, varying from a low (±SD) of 7.19±1.79 mol/ml in the 0.5 MAC halothane group to a high of 12.68±3.65 mol/ml in the 2.0 MAC isoflurane group. End-ischemic brain lactate correlated with preischemic plasma glucose (r=0.5, =0.5). We conclude that increasing concentration of volatile anesthesia with iv phenylephrine blood pressure support produces higher levels of plasma glucose and brain lactate with cerebral ischemia.     

Plasma xanthine oxidase, superoxide dismutase and glutathione peroxidase activities and uric acid levels in severe and mild pre-eclampsia

The aim of the present study was to measure plasma uric acid (UA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) activities and to evaluate the relationship between these parameters and the severity of pre-eclampsia. Twenty-five pre-eclamptic, 15 healthy pregnant and 15 non-pregnant women were enrolled in this study. Increased mean plasma XO activity was found to be higher in both pre-eclampsia groups than in the healthy pregnant group. Plasma UA levels were the highest in the severe pre-eclampsia group among the study groups. SOD and GSH-Px activities were significantly lower in both pre-eclampsia groups than in the healthy pregnant group (p < 0.005 and p < 0.001, respectively). Increased XO and decreased SOD and GSH-Px activities may contribute to the pathophysiological mechanisms of pre-eclampsia and increased UA may serve a protective role responding to superoxide radicals arising from increased XO activity or other sources in pre-eclampsia.     

Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans

Exercise, insulin-induced hypoglycemia and oral glucose loads (50 g and 100 g) were used to compare the production of malondialdehyde and the activity of antioxidant enzymes in healthy subjects. Twenty male volunteers participated in the study. Exercise consisted of three consecutive work loads on a bicycle ergometer of graded intensity (1.5, 2.0, and 2.5 W/kg, 6 min each). Hypoglycemia was induced by insulin (Actrapid MC Novo, 0.1 IU/kg, i.v.). Oral administration of 50 g and 100 g of glucose was given to elevate plasma glucose. The activity of superoxide dismutase (SOD) was determined in red blood cells, whereas glutathione peroxidase (GSH-Px) activity was measured in whole blood. The concentration of malondialdehyde (MDA) was determined by HPLC, catecholamines were assessed radioenzymatically and glucose was measured by the glucose-oxidase method. Exercise increased MDA concentrations, GSH-Px and SOD activities as well as plasma noradrenaline and adrenaline levels. Insulin hypoglycemia increased plasma adrenaline levels, but the concentrations of MDA and the activities of GSH-Px and SOD were decreased. Hyperglycemia increased plasma MDA concentrations, but the activities of GSH-Px and SOD were significantly higher after a larger dose of glucose only. Plasma catecholamines were unchanged. These results indicate that the transient increase of plasma catecholamine and insulin concentrations did not induce oxidative damage, while glucose already in the low dose was an important triggering factor for oxidative stress.     

Effects of isoflurane, halothane, and enflurane on myocardial flow and energy stores in the perfused rat heart

The effect of three volatile anesthetics (halothane, enflurane, and isoflurane) on coronary flow and metabolic state of isolated rat hearts was studied. These anesthetics are coronary dilators and their effects are dose dependent. At 2 MAC (minimum alveolar concentration), isoflurane, enflurane, and halothane increase coronary flow by 114 +/- 5.9, 93 +/- 6.1, and 77 +/- 6.4%, respectively (p less than 0.001). At these concentrations, they also have a modest but significant metabolic effect causing a 30% reduction in myocardial ATP and phosphocreatine levels, with no significant modification in ADP and AMP concentrations. Energy charge and lactate/pyruvate ratio were also unaffected by these anesthetics. The vascular and metabolic effects were reversible within 2 and 30 min, respectively. Perfusion of the hearts with a Krebs-Henseleit solution without Pi did not interfere with the vascular and the metabolic effect of the anesthetics; however, in this case, ATP and phosphocreatine concentration did not return to control levels after their discontinuation despite full recovery of the vascular effect. These data suggest that the volatile anesthetics have direct coronary vascular and myocardial metabolic effects and that these effects occur independently.     

The inhibition of calcium efflux from rat liver mitochondria by halogenated anesthetics

The halogenated anesthetics halothane, enflurane and isoflurane inhibit the calcium efflux induced by Ruthenium Red in isolated rat liver mitochondria. The extent of the inhibition is higher for enflurane (approximately 50%) than for either isoflurane (approximately 35%) or halothane (approximately 15%), and does not increase significantly between 0.1 and 0.6-1.0 mM anesthetic. Both the mitochondrial respiratory rate and transmembrane electrical potential are unaffected by the halogenated anesthetics concentrations capable to inhibit the efflux of calcium.