Oxidative stress is decreased in off-pump versus on-pump coronary artery surgery

Oxidative stress occurs in patients undergoing coronary artery bypass operation. The aim of this study was to investigate the difference in oxidative stress in off-pump versus on-pump coronary artery bypass surgery. In the present study, in serial blood samples, plasma malondialdehyde (MDA) as index of lipid peroxidation, red blood cells glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured to compare the extent of oxidative stress in 30 patients undergoing OPCAB (off-pump coronary artery bypass grafting), 12 patients undergoing CABG (on-pump coronary artery bypass grafting) and 18 healthy controls. In CABG group, MDA levels increased significantly from 2.87 +/- 0.62 nmol/mL before anesthesia and 2.87 +/- 0.65 nmol/mL after anesthesia to 3.05 +/- 0.66 nmol/mL after ischemia (p < 0.05). Similarly, SOD levels also elevated significantly from 661.58 +/- 78.70 U/g Hb before anesthesia and 659.42 +/- 81.21 U/g Hb anesthesia induction to 678.08 +/- 75.80 U/g Hb after ischemia (p < 0.01, p < 0.01, respectively). In OPCAB group, only SOD levels increased from 581.73 +/- 86.24 U/g Hb anesthesia induction to 590.90 +/- 88.90 U/g Hb after reperfusion (p < 0.05). Glutathione peroxidase levels were not changed according to blood collection times in both of CABG group or OPCAB group (p > 0.05). Our results show that only mild signs of oxidative stress is found after reperfusion in OPCAB operation compared with CABG operation. Further studies are needed in order to confirm this hypothesis.     

17β-Estradiol and Vitamin E Modulates Oxidative Stress-Induced Kidney Toxicity in Diabetic Ovariectomized Rat

The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40?μg?kg(-1)/day) and alpha-tocopherol (100?μg?kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4?weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.     

Oral alpha-tocopherol supplementation inhibits lipid oxidation in established human atherosclerotic lesions

BACKGROUND: Much experimental evidence suggests that lipid oxidation is important in atherogenesis and in epidemiological studies dietary antioxidants appear protective against cardiovascular events. However, most large clinical trials failed to demonstrate benefit of oral antioxidant vitamin supplementation in high-risk subjects. This paradox questions whether ingestion of antioxidant vitamins significantly affects lipid oxidation within established atherosclerotic lesions. METHODS AND RESULTS: This placebo-controlled, double blind study of 104 carotid endarterectomy patients determined the effects of short-term alpha-tocopherol supplementation (500 IU/day) on lipid oxidation in plasma and advanced atherosclerotic lesions. In the 53 patients who received alpha-tocopherol there was a significant increase in plasma alpha-tocopherol concentrations (from 32.66 +/- 13.11 at baseline to 38.31 +/- 13.87 (mean +/- SD) micromol/l, p < 0.01), a 40% increase (compared with placebo patients) in circulating LDL-associated alpha-tocopherol (p < 0.0001), and their LDL was less susceptible to ex vivo oxidation than that of the placebo group (lag phase 115.3 +/- 28.2 and 104.4 +/- 15.7 min respectively, p < 0.02). Although the mean cholesterol-standardised alpha-tocopherol concentration within lesions did not increase, alpha-tocopherol concentrations in lesions correlated significantly with those in plasma, suggesting that plasma alpha-tocopherol levels can influence lesion levels. There was a significant inverse correlation in lesions between cholesterol-standardised levels of alpha-tocopherol and 7beta-hydroxycholesterol, a free radical oxidation product of cholesterol. CONCLUSIONS: These results suggest that within plasma and lesions alpha-tocopherol can act as an antioxidant. They may also explain why studies using < 500 IU alpha-tocopherol/day failed to demonstrate benefit of antioxidant therapy. Better understanding of the pharmacodynamics of oral antioxidants is required to guide future clinical trials.     

Effect of alpha-tocopherol supplementation on plasma homocysteine and oxidative stress in highly trained athletes before and after exhaustive exercise

The interrelationship between physical exercise, antioxidant supplementation, oxidative stress and plasma levels of homocysteine (Hcy) has not been adequately examined. The purpose of this study was to examine the effect of 2 months of vitamin E supplementation (800 IU/day alpha-tocopherol) (E) or placebo (P) in 38 triathletes on plasma Hcy concentrations, antioxidant potential and oxidative stress. It was hypothesized that vitamin E supplementation would reduce plasma Hcy and oxidative stress markers compared to placebo. Blood samples were collected 1 day prior to the race, immediately postrace and 1.5 h postrace. Plasma alpha-tocopherol was 75% higher (P<.001) in E versus P prerace (24.1+/-1.1 and 13.8+/-1.1 micromol/L, respectively), and this group difference was maintained throughout the race. Cortisol was significantly increased in both E and P (P<.001), but there was no difference in the pattern of change. There were no significant time, group or interaction effects on plasma Hcy concentrations between E and P. Plasma F(2)-isoprostanes increased 181% versus 97% during the race in E versus P, and lipid hydroperoxides were significantly elevated (P=.009) 1.5 h postrace in E versus P. Plasma antioxidant potential was significantly higher 1.5 h postrace in E versus P (P=.039). This study indicates that prolonged large doses of alpha-tocopherol supplementation did not affect plasma Hcy concentrations and exhibited pro-oxidant characteristics in highly trained athletes during exhaustive exercise.     

Effects of vitamin E and C supplementation either alone or in combination on exercise-induced lipid peroxidation in trained cyclists

Seven trained male cyclists (ate 22.3 +/- 2 years) participated in 4 separate supplementation phases. They ingested 2 capsules per day containing the following treatments: placebo (placebo plus placebo); vitamin C (1 g per day vitamin C plus placebo); vitamin C and E (1 g per day vitamin C plus 200 IU per kg vitamin E); and vitamin E (400 IU per kg vitamin E plus placebo). The treatment order (placebo, vitamin C, vitamin C and E, and vitamin E) was the same for all subjects. Performance trials consisting of a 60-minute steady state ride (SSR) and a 30-minute performance ride (PR) on Cybex 100 Metabolic cycles were performed after each trial. Workloads of 70% of the VO2max were set for the SSR and PR rides, with pedal rate maintained at 90 rpm (SSR) or self determined (PR). Blood samples (5 ml) were drawn pre- and postexercise and analyzed for malonaldehyde (MDA) and lactic acid. The results indicate that vitamin E treatment was more effective than vitamin C alone or vitamin C and E. Pre-exercise plasma levels of MDA in the vitamin E trial was 39% below the pre-exercise MDA levels of the placebo: 2.94 +/- 0.54 and 4.81 +/- 0.65 micromol per ml, respectively. Plasma MDA following exercise in the vitamin E group was also lower than teh placebo: 4.32 +/- 0.37 vs 7.89 +/- 1.0 micromol per ml, respectively. Vitamin C supplementation, on the other hand, elevated both the resting and exercise plasma levels of MDA. None of th supplemental phases had any significant effect on performance. In conclusion, the results indicate that 400 IU/day of vitamin E reduces membrane damage more effectively than vitamin C but does not enhance performance. Athletes are encouraged to include antioxidants, such as vitamin E and C, in their diet to counteract these detrimental effects of exercise. The data presented here suggests that 400 IU/day of vitamin E will provide adequate protection but supplementing the diet with 1 g per day of vitamin C may promote cellular damage. However neither of these vitamins, either alone or in combination, will enhance exercise performance.     

Effect of thinner inhalation on lipid peroxidation and some antioxidant enzymes of people working with paint thinner

Paint thinner is a commonly used industrial solvent with considerable potential for abuse by inhalation. Paint thinner is taken into the body by inhalation or by contact with the skin. Paint thinner is oxidized gradually by cytochrome P450-dependent monooxygenase and consequently free radicals are produced. In the present study we measured plasma malondialdehyde (MDA, a product of lipid peroxidation) levels as an indicator of oxidative damage and activity levels of antioxidant enzymes gluthatione peroxidase (GSH-Px) and superoxide dismutase (SOD) in erythrocytes of a group of people (n = 18) working with paint thinner. The control group was composed of 18 healthy adults. There was a statistically significant (p < 0.001) increase in MDA (2.0+/-0.7 nmol ml(-1)) and GSH-Px (86.5+/-16.6 U g(-1) Hb) activity levels in people working with paint thinner compared with control subjects (MDA: 1.0+/-0.3 nmol ml(-1); GSH-Px: 53.9+/-14.5 U g(-1) Hb). Similarly, there was also an increase (p < 0.05) in the SOD levels (1079+/-214.6 U g(-1) Hb) of people working with paint thinner compared with controls (953.3+/-46.7 U g(-1) Hb). Based on our results, it can be concluded that paint thinner inhalation may increase lipid peroxidation and consequently induce antioxidant enzymes.     

Serum ex vivo lipoprotein oxidizability in patients with ischemic heart disease supplemented with vitamin E

The decreased oxidizability of plasma lipoproteins is related to the increased vitamin E intake and its association with a relatively lower incidence of coronary heart disease has been proposed. We investigated the effect of the in vivo vitamin E supplementation on the oxidizability of serum lipids in patients with ischemic heart disease and a moderate hypercholesterolemia. Thirty-two patients (16 males and 16 postmenopausal women) participated in this placebo-controlled, randomized trial. They were treated with 400 mg vitamin E/day for 6 weeks. The copper-induced serum lipid oxidizability ex vivo was assessed by measuring conjugated diene formation at 245 nm. We also measured vitamin E, malondialdehyde (MDA) and uric acid concentrations in the plasma. Because of observed significant differences in parameters of serum lipid oxidizability (lag time and maximal rate of oxidation), plasma alpha-tocopherol and MDA levels between male patients and postmenopausal women supplemented with vitamin E, the results were compared between both genders. Six weeks of vitamin E supplementation significantly increased plasma vitamin E levels (by 87 %) in male patients but in postmenopausal women only by 34 %. Concomitantly with increased plasma levels of vitamin E the decrease in plasma MDA levels was observed in male patients (decrease by 20 %; p=0.008), but in postmenopausal women the decrease did not attain statistical significance. Plasma uric acid levels were not apparently changed in placebo or vitamin E supplemented groups of patients. The changes in ex vivo serum lipid oxidizability after vitamin E, supplementation have shown a significantly prolonged lag time (by 11 %; p=0.048) and lowered rate of lipid oxidation (by 21 %; p=0.004) in male patients in comparison with postmenopausal women. Linear regression analysis revealed a significant correlation between plasma vitamin E levels and the lag time (r=0.77; p=0.03) and the maximal rate of serum lipid oxidation (r=-0.70; p=0.05) in male patients. However, in postmenopausal women the correlations were not significant. We conclude that 400 mg vitamin E/day supplementation in patients with ischemic heart disease and a moderate hypercholesterolemia influenced favorably ex vivo serum lipid oxidation of male patients when compared with postmenopausal women. The observed differences between both genders could be useful in the selection of the effective vitamin E doses in the prevention of coronary heart disease.     

The association between oxidative stress and obstructive lung impairment in patients with COPD

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.     

Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation.

Twelve clinically healthy subjects participated in a vitamin E supplementation study. Eight were given daily dosages of 150, 225, 800, or 1200 IU RRR-alpha-tocopherol for 21 days (two persons per dose) and four received placebo. Prior, during, and after the supplementation period, alpha-tocopherol, gamma-tocopherol, and carotenoids were determined in plasma and low density lipoprotein (LDL). The maximum levels of alpha-tocopherol were 1.7- to 2.5-times the baseline values in plasma and 1.7- to 3.1-times in LDL. A high correlation existed between alpha-tocopherol in plasma and LDL. gamma-Tocopherol significantly decreased in plasma and LDL during vitamin E supplementation. No significant influence on the lipoprotein and lipid status and carotenoid levels of the participants occurred throughout the supplementation. The resistance of LDL against copper-mediated oxidation was also measured. The oxidation resistance of LDL was significantly higher during vitamin E supplementation. However, the efficacy of vitamin E in protecting LDL varied from person to person. The statistical evaluation of all data gave a correlation of r2 = 0.51 between alpha-tocopherol in LDL and the oxidation resistance as measured by the length of the lag-phase preceding the oxidation of LDL. No association was seen between levels of carotenoids and vitamin E in plasma and LDL. The present study clearly shows that in humans the oxidation resistance of LDL can be increased by vitamin E supplementation.     

Intermittent hypobaric hypoxia-induced oxidative stress in rat erythrocytes: protective effects of vitamin E, vitamin C, and carnitine

This study was aimed at determining the effect of vitamin E, vitamin C, and carnitine on intermittent hypobaric-hypoxia-induced oxidative stress (OS) in erythrocytes. For this purpose, male Wistar rats of 4 months of age were orally supplemented with one of the antioxidants prior to exposure to altitudes of 5700 m or 6300 m. Hemoglobin (Hb) and OS indices such as osmotic fragility and hemolysis were measured together with lipid peroxidation (LPO) and protein oxidation. The increase in Hb was accompanied by increase in activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) during exposure to both the altitudes without any further elevation by supplements. The extent of reduction in osmotic fragility and hemolysis by vitamin E and carnitine was greater at 6300 m than at 5700 m. Increase in LPO products, for example, malondialdehyde (MDA) and lipofuscin-like autofluorescent substances (AFS) was noticeable at both the altitudes, and vitamin E and carnitine were effective in reducing LPO. While protein oxidation products such as carbonyl content (PrC) and advanced oxidation protein products (AOPP) increased at 6300 m, protein sulphydryl (P-SH) content decreased. P-SH levels were restored on supplementation of antioxidants. Hence, our results indicate that vitamin E, vitamin C, and carnitine may be beneficial in overcoming OS and hemolysis under situations such as intermittent hypobaric hypoxia (IHH) and hypobarotherapy wherein hypoxia is used to correct many pathological situations in humans. Further, this study suggests that supplementation of vitamin E, vitamin C, and L-carnitine alone and not in combination can be beneficial in attenuating the OS associated with IHH compared to the unsupplemented rats exposed to two different altitudes.     

Antioxidant activity and metabolite profile of quercetin in vitamin-E-depleted rats

Dietary antioxidants interact in a dynamic fashion, including recycling and sparing one another, to decrease oxidative stress. Limited information is available regarding the interrelationships in vivo between quercetin and vitamin E. We investigated the antioxidant activity and metabolism of quercetin (Q) in 65 F-344 rats (n=13 per group) randomly assigned to the following vitamin E (VE)-replete and -deficient diets: (a) VE replete (30 mg alpha-tocopherol acetate/kg diet) control ad libitum (C-AL), (b) VE replete pair fed (C-PF), (c) VE replete+5.0 g Q/kg diet (R-VE+5Q), (d) VE deplete (<1 mg/kg total tocopherols)+5.0 g Q/kg diet (D-VE+5Q) and (e) D-VE. After 12 weeks, blood and tissue were collected for measurement of plasma vitamin E, quercetin and its metabolites, serum pyruvate kinase (PK), plasma protein carbonyls, malondialdehyde (MDA) and oxygen radical absorbance capacity. D-VE diets decreased serum alpha-tocopherol and increased PK activity in a time-dependent manner. The D-VE diet increased plasma protein carbonyls but did not affect MDA. Dietary quercetin supplementation increased quercetin and its metabolites in plasma and liver but did not affect D-VE-induced changes in plasma alpha-tocopherol, PK or protein carbonyls. Plasma isorhamnetin and its disposition in muscle were enhanced by the D-VE diet, as compared to the R-VE diet. Conversely, tamarixetin disposition in muscle was decreased by the D-VE diet. Thus, quercetin did not slow vitamin E decline in vivo; neither did it provide antioxidant activity in vitamin-E-depleted rats. However, vitamin E status appears to enhance the distribution of isorhamnetin into the circulation and its disposition in muscle.     

Protective effect of alpha-tocopherol on oxidative stress in experimental pulmonary fibrosis in rats

The study was undertaken to investigate the influence of alpha-tocopherol (vitamin E) on malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activity in lung of rats with bleomycin-induced pulmonary fibrosis (PF). Fourteen Wistar-albino rats were randomly divided into two groups of seven animals each. The first group was treated intra-tracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of alpha-tocopherol twice a week (BM + E group). The third group was treated in the same manner with saline solution only, acting as controls (C). There were decreases in GSH level and CAT activity while an increase in MDA level in BM group was found compared to the control group (p < 0.05). Vitamin E had a regulator effect on these parameters. After administration of alpha-tocopherol, the increase in GSH level and CAT activity and the decrease in MDA level were seen in BM + E group compared to BM group (p < 0.05). Distinct histopathological changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM + E group. The results show that vitamin E is effective on the prevention of BM-induced PF, as indicated by differences in the lung levels of oxidants and antioxidants.     

Plasma antioxidants in pediatric patients with glycogen storage disease,diabetes mellitus,and hypercholesterolemia

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20). We measured the total radical-trapping antioxidant parameter (TRAP), single antioxidants (sulfhydryl groups, uric acid, vitamin C, alpha-tocopherol, coenzyme Q10), malondialdehyde, oxidized low density lipoprotein (LDL) antibodies, lipid profile [cholesterol, triglyceride, lipoprotein (a)], homocysteine, and hemoglobin (Hb)A(1C). TRAP levels were elevated in the GSD Ia group (p <.01) and correlated with elevated uric acid levels (r = 0.72, p =.001). None of the other plasma antioxidants correlated with TRAP levels. DMI patients showed decreased sulfhydryl groups (p <.01) and a reduced ubiquinol-10 fraction (p <.01). Malondialdehyde (p <.001) and oxidized LDL autoantibodies (p <.05) were increased in the diabetic group. In FH patients, parameters of oxidative stress and TRAP did not differ from controls. We conclude that in GSD Ia an increased antioxidative defense in plasma may protect against lipid peroxidation and thus against premature atherosclerosis. Furthermore, we demonstrated that in DMI increased oxidative mechanisms are already present in childhood.     

Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits.

Oxidized low-density lipoproteins (LDL) are implicated in atherosclerosis. However, large-scale intervention studies designed to test whether antioxidants, such as vitamin E, can ameliorate cardiovascular disease have generated ambivalent results. This may relate to the fact that the mechanism whereby lipid oxidation is initiated in vivo is unknown and the lack of direct evidence for a deficiency of antioxidants in atherosclerotic lesions. Further, there is little evidence to suggest that vitamin E acts as an antioxidant for lipid peroxidation in vivo. Here we tested the antioxidant effect of dietary vitamin E (alpha-tocopherol) supplementation on intimal proliferation and lipid oxidation in balloon-injured, hypercholesterolemic rabbits. alpha-Tocopherol supplementation increased vascular content of alpha-tocopherol over 30-fold compared to nonsupplemented and alpha-tocopherol-deficient chows. Balloon injury resulted in oxidized lipid deposition in the aorta. Maximum levels of primary lipid oxidation products, measured as hydroperoxides of esterified lipid (LOOH) and oxidized linoleate (HODE), were 0.22 and 1.10 nmol/mg, representing 0.21 and 0.39% of the precursor molecule, respectively. Secondary lipid oxidation products, measured as oxysterols, were maximal at 5.60 nmol/mg or 1.48% of the precursor compound. Vascular HODE and oxysterols were significantly reduced by vitamin E supplementation. However, the intima/media ratio of aortic vessels increased with vitamin E supplementation, suggesting that the antioxidant promoted intimal proliferation. Thus, the study demonstrates a dissociation of aortic lipid oxidation and lesion development, and suggests that vitamin E does not prevent lesion development in this animal model.     

Estimation of lipoperoxidative damage and antioxidant status in diabetic children: relationship with individual antioxidants

Increased oxidative stress has emerged as a potential mechanism implicated in the pathogenesis, progression and cell dysfunction associated with many diseases including diabetes. In routine clinical practice, the estimation of the degree of oxidative damage and antioxidant status, even in paediatric patients, by appropriate techniques appears to be of interest. The aim of this study was to reliably identify patients with increased oxidant stress and/or reduced antioxidant defence mechanisms with a small blood sample and verify the applicability to the study of diabetic children (DC) at clinical onset of the disease. In 1-ml blood samples from 30 DC and 34 controls, techniques for accurately measuring malondialdehyde (MDA) concentrations in plasma and erythrocytes (using HPLC analysis with fluorometric detection), total radical antioxidant potential (TRAP) and blood plasma oxidizability were adapted and validated. Plasma alpha-tocopherol (HPLC), uric acid and sulfhydryl (SH) groups were also determined. At clinical onset of diabetes a significant reduction in plasma TRAP values (P<0.01) was observed in DC compared with controls. Similarly, a significant fall in individual antioxidant levels (alpha-tocopherol/total lipids, uric acid and protein SH) was noted in plasma of DC. Highly significant increases were found in both plasma and erythrocyte MDA levels in DC (p-MDA:1.7+/-0.2 microM; er-MDA: 7.2+/-0.7 nmol/g Hb) compared with controls (p-MDA:0.86+/-0.09 microM; P<0.0003; er-MDA:3.8+/-0.2 nmol/g Hb, P<0.0001). Plasma MDA and triglyceride levels correlated directly only in DC (P<0.001). Whole plasma oxidizability was significantly higher in DC than in controls (P<0.0001) and this parameter correlated significantly with plasma cholesterol and triglyceride concentrations (P<0.0001). The micromethods adapted and applied to the simultaneous detection of lipid peroxidation products and antioxidant status permit accurate and reliable assessment of the oxidative stress process in small plasma samples. Our results clearly show systemic peroxidative damage associated with insufficient defence mechanisms against ROS to be already present at clinical onset of type 1 diabetes mellitus in children and adolescents.     

Effect of vitamin E supplementation on diabetes induced oxidative stress in experimental diabetes in rats

Diabetes induced by streptozotocin (50 mg/kg body wt, i.p.) in the rats substantially increased the plasma glucose and malondialdehyde levels along with corresponding decrease in the antioxidants levels. Supplementation of vitamin E (200 mg/kg body wt., ip) for 5 weeks resulted in non-significant decrease in the blood glucose levels but plasma malondialdehyde levels were reduced to below normal levels. Plasma vitamin E, vitamin C, uric acid and red blood cell glutathione levels were also restored to near normal levels on vitamin E supplementation to diabetic rats as compared to control (diabetic) rats. The activities of antioxidant enzymes, catalase (EC 1.11.1.6), glutathione peroxidase (GSHPx EC 1.11.1.9), and glutathione reductase (GR EC 1.6.4.2) were also concomitantly restored to near normal levels by vitamin E supplementation to diabetic rats. The results clearly demonstrated that vitamin E supplementation augments the antioxidant defense mechanism in diabetes and provides evidence that vitamin E may have a therapeutic role in free radical mediated diseases.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

Antioxidant effect of vitamin E and glutathione on lipid peroxidation in boar semen plasma

The protective effect of vitamin E and reduced glutathione (GSH) against lipid peroxidation in boar semen plasma was studied. The lipid peroxidation, measured by the test for thiobarbituric acid reactive substances (TBARS), doubled in the presence of the lipid peroxidation Fe²⁺-sodium ascorbate-inducing system. The ascorbate-induced TBARS were inhibited by about 62% through the water-soluble vitamin E analog (TROLOX) and about 57% by GSH. In the in vivo experiments, 7 wk of oraldl-α-tocopherol acetate (1000 IU/d/animal) administration caused a significant fall in the level of the semen plasma TBARS, from 2.2±0.09 to 1.2±0.13 nmol MDA/mL. The semen plasma superoxide dismutase (SOD) and GSSG tended to increase with the time of vitamin E administration, but the increment did not reach a significant level by the seventh week. The vitamin E supplementation significantly increased the number of spermatozoa per 1 cm³ of ejaculate. The protective role of vitamin E and GSH with respect to boar semen against fatty acid peroxidation and a positive influence of vitamin E supplementation on semen quality have been evidenced.     

Alpha-tocopherol supplementation does not affect monocyte endothelial adhesion or C-reactive protein levels but reduces soluble vascular adhesion molecule-1 in the plasma of healthy subjects

Vascular monocyte retention in the subintima is pivotal to the development of cardiovascular disease and is facilitated by up-regulation of adhesion molecules on monocytes/endothelial cells during oxidative stress. Epidemiological studies have shown that cardiovascular disease risk is inversely proportional to plasma levels of the dietary micronutrients, vitamin C and vitamin E (alpha-tocopherol). We have tested the hypothesis that alpha-tocopherol supplementation may alter endothelial/monocyte function and interaction in subjects with normal ascorbate levels (> 50 microM), as ascorbate has been shown to regenerate tocopherol from its oxidised tocopheroxyl radical form in vitro. Healthy male subjects received alpha-tocopherol supplements (400 IU RRR-alpha-tocopherol/day for 6 weeks) in a placebo-controlled, double-blind intervention study. There were no significant differences in monocyte CD11b expression, monocyte adhesion to endothelial cells, plasma C-reactive protein or sICAM-1 concentrations post-supplementation. There was no evidence for nuclear translocation of NF-kappaB in isolated resting monocytes, nor any effect of alpha-tocopherol supplementation. However, post-supplementation, sVCAM-1 levels were decreased in all subjects and sE-selectin levels were increased in the vitamin C-replete group only; a weak positive correlation was observed between sE-selectin and alpha-tocopherol concentration. In conclusion, alpha-tocopherol supplementation had little effect on cardiovascular disease risk factors in healthy subjects and the effects of tocopherol were not consistently affected by plasma vitamin C concentration.     

Breath alkanes as a marker of oxidative stress in different clinical conditions

We assessed oxidative stress in three different clinical conditions: smoking, human immunodeficiency virus (HIV) infection, and inflammatory bowel disease, using breath alkane output and other lipid peroxidation parameters such as plasma lipid peroxides (LPO) and malondialdehyde (MDA). Antioxidant micronutrients such as selenium, vitamin E, C, beta-carotene and carotenoids were also measured. Lipid peroxidation was significantly higher and antioxidant vitamins significantly lower in smokers compared to nonsmokers. Beta-carotene or vitamin E supplementation significantly reduced lipid peroxidation in that population. However, vitamin C supplementation had no effect. In HIV-infected subjects, lipid peroxidation parameters were also elevated and antioxidant vitamins reduced compared to seronegative controls. Vitamin E and C supplementation resulted in a significant decrease in lipid peroxidation with a trend toward a reduction in viral load. In patients with inflammatory bowel disease, breath alkane output was also significantly elevated when compared to healthy controls. A trial with vitamin E and C is underway. In conclusion, breath alkane output, plasma LPO and MDA are elevated in certain clinical conditions such as smoking, HIV infection, and inflammatory bowel disease. This is associated with lower levels of antioxidant micronutrients. Supplementation with antioxidant vitamins significantly reduced these lipid peroxidation parameters. The results suggest that these measures are good markers for lipid peroxidation.