Redox status and lipid peroxidation in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes

Background: Free radical-mediated oxidative stress has been implicated in the progression of alcoholic hypertension and diabetic hypertension. Methods: The lipid peroxides and antioxidant status of plasma and erythrocytes were investigated in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes and compared with normal subjects. Results: A significant increase is observed in the levels of glucose, lipid peroxidation (P<0.05) in the alcoholic hypertensive patients with/without diabetes and the increase was significantly higher in alcoholic hypertensive patients with diabetes. The activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) and plasma concentrations of GSH, vitamin C, vitamin E and β-carotene decreased significantly and the level of ceruloplasmin increased in alcoholic hypertensive patients with/without diabetes when compared to normal subjects. Plasma GSH and vitamin E levels exhibited a further decrease in alcoholic hypertensive patients with diabetes. Conclusions: An enhanced lipid peroxidation is observed in alcoholic hypertensive patients with diabetes and a more pronounced decrease in the levels of plasma GSH and vitamin E among antioxidants.     

Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes.

OBJECTIVE: To determine the effect of 400 IU/day of the antioxidant vitamin E on the susceptibility of plasma LDL and lymphocyte DNA to oxidative damage in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 42 patients with type 1 diabetes and 31 age- and sex-matched control subjects in a randomized prospective double-blind placebo-controlled trial by using 400 IU/day of oral vitamin E for 8 weeks. Measurements were made of single-strand breaks in lymphocyte DNA at baseline and after hydrogen peroxide-induced stress (comet assay) and of copper-induced LDL oxidization and plasma antioxidant profiles. RESULTS: Plasma LDL and lymphocyte DNA were more resistant to induced oxidative change in the type 1 diabetes group than in control subjects. Vitamin E supplementation reduced LDL oxidizability in the control subjects but not in the type 1 diabetes group and had no effect on oxidative DNA damage in either group. The type 1 diabetes group had a significantly poorer plasma antioxidant profile with lower mean serum concentrations of alpha-tocopherol and most carotenoids than control subjects. CONCLUSIONS: Plasma LDL and lymphocyte DNA appear to be more resistant to oxidative change in type 1 diabetic subjects than in control subjects, and there was no evidence of oxidatively induced DNA or LDL change in type 1 diabetes. This study does not support the hypothesis of oxidative damage in these patients, and a dose of vitamin E (400 IU/day) that reduced LDL oxidative susceptibility in control subjects did not do so in patients with type 1 diabetes.     

Plasma F2 isoprostanes: direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes

OBJECTIVES: Acute hyperglycemia in type 2 diabetes increases the generation of plasma 8-epi-prostaglandin F2 (8-epi-PGF2alpha) isoprostane, a sensitive direct marker of in vivo free radical oxidative damage to membrane phospholipids. RESEARCH DESIGN AND METHODS: A total of 21 patients with type 2 diabetes underwent an oral 75-g glucose tolerance test. Plasma 8-epi-PGF2alpha isoprostane concentrations (by gas chromatography [GC]/mass spectrometry [MS]), intralymphocyte reduced-to-oxidized glutathione ratios, and plasma total antioxidant capacity were measured at baseline and 90 min after glucose loading. RESULTS: Plasma 8-epi-PGF2alpha isoprostane concentrations rose significantly (P=0. 010) from 0.241 +/- 0.1 to 0.326 +/- 0.17 ng/l after 90 min. Intracellular oxidative balance and plasma antioxidant capacity did not change in either group. CONCLUSIONS: Plasma concentrations of 8-epi-PGF2alpha isoprostane increase during acute hyperglycemia in type 2 diabetes, providing direct evidence of free radical-mediated oxidative damage and demonstrating a pathway for an association between acute rather than fasting hyperglycemia and macrovascular risk in type 2 diabetes.     

Oxidative stress and antioxidants in epilepsy

In the present study, erythrocyte membrane lipid peroxidation, the percentage hemolysis, erythrocyte enzymes superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), catalase, and plasma vitamin C, vitamin E, vitamin A and ceruloplasmin activities and concentrations were determined in 29 epileptic patients and 50 normal controls. Ten patients who were treated with phenobarbital and who did not get convulsions for 1 year were considered for followup. Lipid peroxidation and percentage hemolysis in patients with epilepsy was significantly higher when compared to controls. Moreover, plasma ceruloplasmin concentrations were also markedly increased in these cases. Erythrocyte GR and plasma vitamin C and A concentrations were significantly lower in epileptics when compared to controls. In the followup patients, the erythrocyte GR was significantly higher than their pre-treated condition. Furthermore, the plasma vitamin A, E and C concentrations have attained the normal range. This study indicates that the antioxidant status in blood of epileptic patients which was low compared to controls, improved after treatment, suggesting that free radicals may be implicated in epilepsy.     

Circulating monocyte chemoattractant protein-1 and early development of nephropathy in type 1 diabetes

OBJECTIVES: To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment. RESULTS: FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values. CONCLUSIONS: This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.     

Evidence of oxidative stress in the circulation of ovarian cancer patients

BACKGROUND: Ovarian cancer is the leading cause of death due to gynecological malignancies among women. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant mechanisms. The present study was conducted to investigate the extent of oxidative stress and the levels of antioxidants in the circulation of ovarian cancer patients. METHODS: Plasma thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), vitamin C and vitamin E were estimated in the circulation of 30 ovarian cancer patients and an equal number of age-matched normal subjects as control. RESULTS: Significantly increased concentrations of plasma TBARS and CD and significantly lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian cancer patients as compared with normal subjects. CONCLUSION: The low levels of SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Increased levels of lipid peroxidation may be due to excessive oxidative stress caused by incessant ovulation or epithelial inflammation.     

Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects

The purpose of this study was to investigate the effect of eicosapentaenoic and docosahexaenoic acids on plasma lipids and lipoproteins, lipid peroxidation and antioxidant status in healthy humans. A total of 19 healthy volunteers consumed 6 g/day Maxepa® fish oil for 3 weeks (1.8 g n-3 fatty acids/day). At baseline and at day 21, we evaluated plasma lipoproteins, plasma and low-density lipoprotein fatty acids, lipid peroxidation markers (malondialdehyde concentration, low-density lipoprotein peroxidation in vitro), and the content of a number of antioxidants (reduced and oxidized glutathione in whole blood, plasma and erythrocyte glutathione peroxidases, plasma vitamin E and beta carotene). Plasma concentrations of total cholesterol, triglycerides, phospholipids, low-density lipoprotein cholesterol and low-density lipoprotein size did not differ significantly after 3 weeks of supplementation. Adding the fish oil to the diet increased the concentration of n-3 very-long-chain polyunsaturated fatty acids and decreased the concentration of n-6 fatty acid and oleic acid in plasma and low-density lipoprotein. Eicosapentaenoic and docosahexaenoic acid supplementation caused elevated values of the high-density lipoprotein cholesterol due to an increment of the high-density lipoprotein 2 fraction and reduced low-density lipoprotein peroxidation rate in vitro. However, we observed an imbalance between oxidizable substrates and antioxidants with an increased lipid peroxidation, whereas the content of reduced glutathione and beta carotene decreased without any variation in vitamin E. Association of antioxidants with n-3 PUFA could prevent lipid peroxidation and enhance the antiatherogenic effects of n-3 polyunsaturated fatty acids.     

Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects.

The purpose of this study was to investigate the effect of eicosapentaenoic and docosahexaenoic acids on plasma lipids and lipoproteins, lipid peroxidation and antioxidant status in healthy humans. A total of 19 healthy volunteers consumed 6 g/day Maxepa fish oil for 3 weeks (1.8 g n-3 fatty acids/day). At baseline and at day 21, we evaluated plasma lipoproteins, plasma and low-density lipoprotein fatty acids, lipid peroxidation markers (malondialdehyde concentration, low-density lipoprotein peroxidation in vitro), and the content of a number of antioxidants (reduced and oxidized glutathione in whole blood, plasma and erythrocyte glutathione peroxidases, plasma vitamin E and beta carotene). Plasma concentrations of total cholesterol, triglycerides, phospholipids, low-density lipoprotein cholesterol and low-density lipoprotein size did not differ significantly after 3 weeks of supplementation. Adding the fish oil to the diet increased the concentration of n-3 very-long-chain polyunsaturated fatty acids and decreased the concentration of n-6 fatty acid and oleic acid in plasma and low-density lipoprotein. Eicosapentaenoic and docosahexaenoic acid supplementation caused elevated values of the high-density lipoprotein cholesterol due to an increment of the high-density lipoprotein 2 fraction and reduced low-density lipoprotein peroxidation rate in vitro. However, we observed an imbalance between oxidizable substrates and antioxidants with an increased lipid peroxidation, whereas the content of reduced glutathione and beta carotene decreased without any variation in vitamin E. Association of antioxidants with n-3 PUFA could prevent lipid peroxidation and enhance the antiatherogenic effects of n-3 polyunsaturated fatty acids.     

Lipid profile, oxidant-antioxidant status and glycoprotein components in hyperlipidemic patients with/without diabetes

BACKGROUND: Plasma lipoproteins are protected against oxidative modification by the antioxidant defense system. An imbalance in the antioxidant defense system seems to result from the accumulation of low density lipoprotein (or) very low density lipoprotein in the course of hyperlipidemia. METHODS: The lipid profile, glycoprotein components, glucose, total proteins, albumin, lipid peroxidation and antioxidant status of plasma and erythrocytes were investigated in hyperlipidemic patients and hyperlipidemic patients with diabetes on treatment with glibenclamide (or) glipizide along with normal subjects and compared. RESULTS: A significant increase was observed in the levels of total cholesterol (TC), VLDL-C, triglycerides (TG), lipid peroxidation, ceruloplasmin (CP), glycoprotein components and glucose in the hyperlipidemic patients with/without diabetes and the increase was more pronounced (except TC) in patients with diabetes. The activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and plasma concentrations of vitamins C and E, and reduced glutathione (GSH) decreased in hyperlipidemic patients with/without diabetes. GPx, CAT, vitamin C and GSH levels exhibited a further decrease in hyperlipidemic patients with diabetes. CONCLUSION: An enhanced levels of VLDL-C, TC/HDL-C ratio, TG, lipid peroxidation, glycoprotein components, and decreased concentrations of total proteins (TPs) and albumin were observed in hyperlipidemic patients with diabetes while the decrease was more marked in GSH, vitamin C, CAT and GPx among antioxidants.     

Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes

OBJECTIVES: To evaluate oxidative and antioxidative status in pregnant diabetic women between 26 and 32 weeks of gestation. DESIGN AND METHODS: Free and total malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and vitamins A and E were determined in plasma and erythrocytes of 54 pregnant women. Among these, 27 were diabetics with either gestational diabetes mellitus (GDM), sub-group I, or previous insulin-dependent diabetes mellitus (type 1 diabetes), sub-group II. The other 27 patients were controls. Fasting plasma glucose and HbA(1c) levels were determined in all women. RESULTS: HbA(1c) levels, plasma-, and erythrocyte-free MDA levels were significantly higher in all diabetic women and in both sub-groups than in controls. Plasma vitamin E and erythrocyte vitamin A levels were significantly lower in all diabetic women than in controls. Moreover, GPX and SOD activities were significantly reduced in all diabetic women, GPX in both sub-groups and SOD only in type 1 diabetes. CONCLUSIONS: The increased oxidative stress we demonstrated in pregnant women with previous type 1 diabetes or with GDM should be monitored by strictly controlling blood glucose during pregnancy with stringent recommendations and perhaps antioxidant supplementation.     

Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects

OBJECTIVE: Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS: Eighty overweight individuals (BMI >27 kg/m(2)) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months. RESULTS: Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period. CONCLUSIONS: In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient.     

The evaluation of altered redox status in plasma and mitochondria of acute and chronic diabetic rats

OBJECTIVES: An increase in plasma oxidative stress and decreased mitochondrial lipid hydroperoxides may contribute to the imbalance in the redox status between intramitochondrial and extramitochondrial milieu in chronic experimental diabetic rats. DESIGN AND METHODS: To determine the effect of hyperglycemia in promoting redox imbalance, we determined lipid hydroperoxides (LHP), protein carbonyl (PCO), total antioxidant activity (ferric reducing/antioxidant power; FRAP) and albumin as markers of redox status of plasma, and mitochondrial lipid hydroperoxide levels as a marker of lipid peroxidation in liver, pancreas and kidney tissue of acute and chronic diabetic male Sprague-Dawley rats and their controls. The levels of the studied markers were determined by colorimetric methods. RESULTS: Plasma and mitochondrial oxidative stress parameter levels of acute diabetic rats were not significantly different from their controls. Plasma LHP and PCO levels of chronic diabetic rats were increased significantly as compared to those of both acute diabetic rats and the controls. Plasma FRAP levels of chronic diabetic animals were decreased significantly as compared to those of the controls. On the other hand, LHP levels in liver, pancreas and kidney mitochondria of chronic diabetic rats were decreased significantly as compared to those of both acute diabetic rats and the controls. We observed a negative correlation between LHP levels in liver mitochondria of chronic diabetic rats, and PCO and fructosamine levels in plasma of chronic diabetic rats were correlated. LHP levels in the pancreatic mitochondria of chronic diabetic rats and plasma oxidative stress parameters of chronic diabetic rats were not significantly correlated. LHP levels in kidney mitochondria of chronic diabetic rats were significantly correlated with serum albumin. There was no correlation between LHP levels in kidney mitochondria and other plasma oxidative stress parameters in chronic diabetic rats. CONCLUSIONS: Our data suggest that redox imbalance between plasma and liver mitochondria might become a major threat to chronic diabetic rats.     

Blood oxidative stress status in patients with macrophagic myofasciitis.

The study aimed at determining the presence of an oxidative stress in patients with macrophagic myofasciitis (MMF), a new inflammatory myopathy with suspected toxic etiology related to aluminium hydroxide-containing vaccines. A total of 30 MMF patients (nine males, 21 females; aged 42+/-14 years), whose diagnosis was confirmed by deltoid biopsy, have been included and compared to 38 sex- and age-matched healthy control subjects (10 males, 28 females; aged 43+/-8 years). The blood oxidative stress status has been evaluated by assaying six parameters: plasma lipid peroxidation products (thiobarbituric acid-reactive substances: TBARS) and antioxidant defense systems: plasma vitamin E and glutathione peroxidase (GSH-Px) activity, erythrocyte GSH-Px and Cu,Zn-superoxide dismutase (SOD) activities. Plasma selenium was also determined as a trace element essential to the activity of GSH-Px. Statistical significance was evaluated by the Mann-Whitney test. Plasma GSH-Px activity, selenium and vitamin E concentration were significantly lower in MMF group than in controls (P=0.004, P=0.003 and P=0.009, respectively), with a positive correlation in MMF patients between plasma GSH-Px activity and selenium concentration (rho=0.0001). The other parameters of oxidative stress did not significantly differ between both groups. A macrophage activation could occur in MMF, consequently to chronic stimulation by aluminium-containing vaccines, and could participate to the lower values of selenium and vitamin E observed in comparison with controls. Nevertheless, since no deficiency in these elements has been observed, no supplementation is to be considered.     

Decreased deformability of donor red blood cells after intrauterine transfusion in the human fetus: possible reason for their reduced life span?

BACKGROUND: The life span of donor red blood cells (RBCs) is reduced in the fetus with Rh hemolytic disease. This may have resulted from donor or recipient factors. STUDY DESIGN AND METHODS: Studied in vitro was the effect of gamma irradiation on hemolysis, methemo-globin (metHb), and lipid peroxidation of donor RBCs and the ability of fetal and adult plasma to protect irradiated RBCs from induced lipid peroxidation. Also studied in vivo were the effects after the time that donor RBCs reside in the fetus by measuring its lipid peroxidation, cholesterol-to-phospholipid ratios, and deformability of RBCs. RESULTS: Irradiation barely increased hemolysis and metHb formation and did not increase lipid peroxidation. Plasma samples of D+ fetuses inhibited induced oxidative stress less than plasma samples of adults. Nevertheless, in vivo lipid peroxidation of the donor RBC membrane had not increased, whereas the molar cholesterol-to-phospholipid ratio increased from 1.08 +/- 0.11 to 1.38 +/- 0.12. It became identical to that of the fetal RBCs (1.44 +/- 0.12). Before transfusion, the deformability of the adult RBCs (elongation index, 0.578 +/- 0.013) was better than that of the fetal cells (elongation index, 0.494 +/- 0.027), but decreased to fetal levels after transfusion (elongation index, 0.518 +/- 0.039). CONCLUSION: Irradiation of the RBCs and a reduced fetal antioxidant capacity do not lead to in vivo lipid peroxidation. The shorter life span of donor cells in the fetus probably results from a decreased deformability of the RBCs after transfusion, most likely owing to an increased cholesterol-to-phospholipid ratio.     

Lack of effect of oral vitamin C on blood pressure,oxidative stress and endothelial function in Type II diabetes

Type II diabetes is characterized by increased oxidative stress, endothelial dysfunction and hypertension. We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes. Subjects ( n =35) received vitamin C (1.5 g daily in three doses) or matching placebo for 3 weeks in a randomized, double-blind, parallel-group design. Plasma concentrations of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), a non-enzymically derived oxidation product of arachidonic acid, were used as a marker of oxidative stress. Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine (with nitroprusside as an endothelium-independent control) and by the pulse wave responses to systemic albuterol (endothelium-dependent vasodilator) and glyceryl trinitrate (endothelium-independent vasodilator). Plasma concentrations of vitamin C increased from 58+/-6 to 122+/-10 micromol/l after vitamin C, but 8-epi-PGF(2alpha) levels (baseline, 95+/-4 pg/l; after treatment, 99+/-5 pg/l), blood pressure (baseline, 141+/-5/80+/-2 mmHg; after treatment, 141+/-5/81+/-3 mmHg) and endothelial function, as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine, were not significantly different from baseline or placebo. Thus treatment with vitamin C (1.5 g daily) for 3 weeks does not significantly improve oxidative stress, blood pressure or endothelial function in patients with Type II diabetes.     

Elevated plasma levels of reduced homocysteine in common variable immunodeficiency — a marker of enhanced oxidative stress

Based on previous studies from our group, we hypothesized that enhanced oxidative stress in association with a persistent immune activation may be important in both the immunopathogenesis and certain clinical manifestations in a subgroup of patients with common variable immunodeficiency (CVI). To explore this hypothesis further, we examined plasma levels of lipid peroxidation, antioxidant vitamins and redox status of various thiol species in 20 CVI patients and 16 healthy control subjects. We found significantly higher malondialdehyde (MDA) levels in plasma from CVI patients than in healthy control subjects. Furthermore, in a subgroup of CVI patients characterized by persistent immune activation in vivo (CVI_Hyper), we found significantly decreased levels of vitamin E and β-carotene. In the CVI patients, there was a significant inverse correlation between MDA levels and levels of vitamin E and β-carotene. Finally, we found a marked elevation in plasma levels of reduced homocysteine in the CVI group, but no corresponding rise in plasma levels of total homocysteine. In the CVI group, the high plasma levels of reduced homocysteine were significantly correlated with enhanced lipid peroxidation and low levels of vitamin E. The results of the present study further support a role for enhanced oxidative stress in the immunopathogenesis of CVI. Furthermore, our finding of markedly elevated plasma levels of reduced homocysteine in CVI patients without simultaneous elevation of other homocysteine species suggests that this disturbance in homocysteine metabolism may be related to enhanced oxidative stress.     

Lipid peroxidation and antioxidative status in beta-thalassemia major patients with or without hepatitis C virus infection.

BACKGROUND: Information pertaining to the lipid peroxidation and antioxidative status of patients with beta-thalassemic major, with or without hepatitis C virus infection, has been scanty. METHODS: We report here the results of our efforts in the evaluation of lipid peroxidative status, antioxidants, and vitamin A, E and C levels in the sera of a group of patients (n=42) with transfusion-dependent beta-thalassemic major with or without HCV infection. RESULTS: Firstly, plasma thiobarbituric acid reactive substance, a lipid peroxidation product, in these patients was found to be increased significantly when compared to the disease-free controls (p<0.05). Conversely, levels of plasma vitamins A, E and C were all shown to be drastically reduced as compared to the disease-free controls (p<0.01). In parallel with these data, we also found that HCV infection did play some role in aggravating the depletion of plasma vitamin E and C levels in the beta-thalassemic patients. In contrast, HCV infection did not seem to alter the levels of reduced glutathione (GSH) as well as antioxidant enzyme activities including superoxide dismutase and GSH peroxidase. CONCLUSIONS: Taken together, our data indicate that excessive lipid peroxidation and a profound depletion of plasma vitamin A, E and C levels exist in patients with beta-thalassemic major. These data suggest that antioxidant supplementation to the patients for the purpose of alleviating the oxidative stress may be warranted.     

Oxidative stress and antioxidant status in patients with alcoholic liver disease

BACKROUND: Alcoholic liver diseases (ALD) are very common in lower socio-economical strata due to heavy drinking habits and multiple nutritional deficiencies. Ethanol causes liver damage by many mechanisms. The generation of lipid peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. These free radicals are destroyed by anti-oxidants. Many anti-oxidants are present in the diet, e.g., vitamin E, vitamin C etc. However, poor nutrition or malabsorption leads to deficiency of these vitamins. This may impair the anti-oxidative defense leading to ethanol induced oxidative stress and then to liver damage. METHODS: Oxidative stress and antioxidant defense were assessed in patients with alcoholic liver disease. Serum malondialdehyde (MDA) concentrations were measured as an index of lipid peroxidation, i.e., oxidative stress; and serum vitamins E and C concentrations were measured as an index of antioxidant status. RESULTS: Serum MDA concentrations were increased with the increase in severity of the disease. Concentrations of serum vitamins E and C were decreased in patients with alcoholic liver disease as compared to controls. CONCLUSIONS: Our observations may be due to increased demands of the same or increased utilization.     

Lipid and protein oxidation and antioxidant status in patients with angiographically proven coronary artery disease

OBJECTIVES: We aimed to evaluate the association of lipid peroxidation, protein oxidation and antioxidant system, and to assess an association with the severity of the disease, in patients with and without coronary artery disease (CAD) documented by coronary angiography. DESIGN AND METHODS: The population included 208 patients, undergoing clinically indicated coronary angiography. While the subjects with normal coronary angiograms (n=54) were evaluated as controls, the patients with CAD (n=154) were divided into three categories according to the number of diseased coronaries; one-vessel (n=50), two-vessels (n=51) and three-vessels (n=53). Lipid parameters were determined by routine laboratory methods. Plasma malondialdehyde and vitamin E concentrations were determined with the high-performance liquid chromatography. Other oxidant and antioxidant parameters were studied spectrophotometrically. RESULTS: While plasma malondialdehyde levels, the susceptibilities of erythrocyte and apolipoprotein B containing lipoproteins to in vitro induced oxidative stress, serum protein carbonyls, low density lipoprotein-cholesterol, triglyceride, apolipoprotein B and lipoprotein (a) levels had significantly increased, high-density lipoprotein-cholesterol and apolipoprotein AI levels, erythrocyte glutathione peroxidase, glutathione reductase, glucose 6 phosphate dehydrogenase, serum catalase, paraoxonase and arylesterase activities, plasma vitamin E and C and carotenoid levels had significantly decreased. The odds ratios for one-, two-, and three-vessel disease increased across especially higher tertiles of concentrations for oxidation parameters and lower tertiles of concentrations for antioxidant parameters. CONCLUSIONS: According to the results, we suggest that increased lipid and protein oxidation products and decreased antioxidant enzymes and vitamins contribute to increased oxidative stress which in turn is related to the severity of the disease.     

Red blood cell susceptibility to lipid peroxidation, membrane lipid composition, and antioxidant enzymes in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: The following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also assayed. PATIENTS: Eleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls. RESULTS: The MDA formation after H2O2 stimulation was normal in CAPD patients (0.79 +/- 0.1 mumol/gHb versus 0.78 +/- 0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (p less than 0.001) and increased monounsaturated fatty acids (p less than 0.001). Both RBC GSH-Px activity, a selenium-dependent enzyme, and serum selenium levels were significantly lower in CAPD patients, and a significant positive correlation (r = 0.68; p less than 0.02) between the two parameters was found. CONCLUSIONS: This study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation.