Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome. Effects of pitavastatin and atorvastatin on lipoprotein oxidation biomarkers in patients with dyslipidemia. The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. Atorvastatin treatment increases plasma bilirubin but not HMOX1 expression in stable angina patients Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina. Effect of soy isoflavone supplementation on vascular endothelial function and oxidative stress in postmenopausal women: a community randomized controlled trial. Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study. N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients--a pilot study. Vascular effects of diet and statin in hypercholesterolemic patients. Combined antioxidant treatment effects on blood oxidative stress after eccentric exercise. Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. Protecting effect of vitamin E supplementation on submaximal exercise-induced oxidative stress in sedentary dogs as assessed by erythrocyte membrane fluidity and paraoxonase-1 activity. SPERM OXIDATIVE STRESS AND THE EFFECT OF AN ORAL VITAMIN E AND SELENIUM SUPPLEMENT ON SEMEN QUALITY IN INFERTILE MEN Oxidative stress improvement is associated with increased levels of taurine in CKD patients undergoing lipid-lowering therapy Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients. Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Preoperative Atorvastatin Treatment in CABG Patients Rapidly Improves Vein Graft Redox State by Inhibition of Rac1 and NADPH-Oxidase Activity Evaluation of Oxidative Stress in Laparoscopic Cholecystectomy Effect of flaxseed oil on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients: a randomized controlled trial Screening for pre-eclampsia by oxidative stress markers and uteroplacental blood flow The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant–antioxidant system in patients with dyslipidemia Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats. Lipid peroxidation, antioxidant status and survival in institutionalised elderly: A five-year longitudinal study Statins as immunomodulators in systemic sclerosis. Effects of different steroid treatment on reperfusion‐associated production of reactive oxygen species and arrhythmias during coronary surgery Oxidative stress responses in older men during endurance training and detraining. Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2 diabetic patients Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo-Oxidation in Master Athletes Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?
BACKGROUND It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome ( PCOS ) .  Statins are considered to have a pleiotropic effect other than their lipid-lowering effect . These effects may be mediated in part by reducing oxidative stress . METHODS This r and omized , double-blind , placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde ( MDA ) concentrations as a marker of oxidative stress in patients with PCOS . Forty medication-naïve patients with PCOS were r and omized to either atorvastatin 20 mg daily or placebo for 3 months . A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo . RESULTS There was a significant decrease of MDA concentrations  with atorvastatin [ mean ( sem ) ] [ 0.29 ( 0.04 ) vs. 0.25 ( 0.02 ) μmol/liter ; P < 0.01 ] compared with placebo [ 0.28 ( 0.02 ) vs. 0.29 ( 0.12 ) μmol/liter ; P = 0.52 ] . Three months treatment with metformin result ed in further reduction of MDA levels  with atorvastatin compared with baseline [ 0.25 ( 0.02 ) baseline vs. 0.23 ( 0.03 ) μmol/liter for atorvastatin treated ; P = 0.02 ] . There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein ( r = 0.71 , P < 0.01 ) , an increase in 25-hydroxyvitamin D ( 25OHD ; r = -0.68 , P = 0.02 ) , and a reduction in testosterone levels ( r = 0.63 , P = 0.01 ) . Multiple linear regression analysis revealed Δ25OHD , ΔC-reactive protein , and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment . No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters . CONCLUSIONS Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone , 25OHD , and high-sensitivity C-reactive protein OBJECTIVE The effects of potent statins on oxidized lipoprotein biomarkers are not well defined . METHODS AND RESULTS The VISION ( Value of oxIdant lipid lowering effect by Statin InterventiON in hypercholesterolemia ) Trial r and omized patients with hypercholesterolemia to 12-week administration of  pitavastatin 2 mg/day ( n = 21 ) or atorvastatin 10 mg/day ( n = 21 ) and a variety of lipoprotein oxidative biomarkers were measured . Between-group analysis did not reveal any differences except in the ratio of malondialdehyde (MDA)-LDL over apolipoprotein B-100 ( MDA-LDL/apoB ) in pitavastatin vs. atorvastatin group ( -13 % vs. -0.7 % , p = 0.04 ) . Within-group changes from baseline to 12-week revealed significant increases in OxPL/apoB and reductions in small-dense LDL , MDA-LDL , and lipoprotein-associated phospholipase A(2 ) measured on circulating apoB particles ( Lp-PLA(2)/apoB ) in both groups and significant reductions in OxPL/apoAI in the atorvastatin group . CONCLUSIONS The VISION study describes the first comparison on lipoprotein oxidation biomarkers between pitavastatin and atorvastatin and suggests diverse effects on lipoprotein oxidation markers in patients with hypercholesterolemia OBJECTIVES The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma . BACKGROUND Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol ( LDL-C ) and cardiovascular risk , but their effects on circulating biomarkers of oxidative stress are not well-defined . METHODS Hypercholesterolemic subjects ( n = 120 , ages 21 to 80 years with LDL-C 130 to 220 mg/dl ) were r and omized in a double-blind , parallel design to pravastatin 40 mg/day ( prava40 ) , atorvastatin 10 mg/day ( atorva10 ) , atorvastatin 80 mg/day ( atorva80 ) , or placebo . At baseline and 16 weeks , urinary isoprostanes ( 8 , 12-iso-iPF(2 alpha)-VI isoform ) , plasma lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , Mercodia oxidized LDL ( OxLDL ) with antibody 4E6 , oxidized phospholipids/apolipoprotein B-100 particle ( OxPL/apoB ) with antibody E06 , immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL , and apolipoprotein B (apoB)-immune complexes ( IC ) were measured . RESULTS After 16 weeks , there were no significant changes in urinary 8 , 12-iso-iPF(2 alpha)-VI . The Lp-PLA2 and OxLDL were reduced in statin-treated groups , but after adjusting for apoB , only prava40 led to a reduction in Lp-PLA2 ( -15 % , p = 0.008 ) and atorva10 to a decrease in OxLDL ( -12.9 % , p = 0.01 ) . The OxPL/apoB increased 25.8 % ( p < 0.01 ) with prava40 and 20.2 % ( p < 0.05 ) with atorva80 . There were no changes in MDA-LDL autoantibodies , but significant decreases in IC were noted . CONCLUSIONS This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects . Future outcome studies should collectively assess various oxidative markers to define clinical utility Abstract Background . In vitro and animal studies indicate that statins increase heme oxygenase-1 gene ( HMOX1 ) expression , which then , presumably , increases plasma bilirubin concentration . However , clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking . We hypothesized that in patients with stable angina  atorvastatin therapy ( 20 mg/day for 10 weeks ) concomitantly increases total bilirubin concentration and HMOX1 expression , as assessed non-invasively by plasma analysis . Methods . In 44 patients with stable angina plasma concentrations of total bilirubin , HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment , as well as plasma concentrations of oxidized low-density lipoprotein ( OxLDL ) , malondialdehyde ( MDA ) , monocyte chemoattractant protein ( MCP-1 ) and C-reactive protein ( CRP ) . Results . Atorvastatin treatment increased total bilirubin concentration ( median 6.95 μmol/L vs. 8.55 , + 23.02 % ; p < 0.001 ) , but did not change plasma HMOX1 mRNA and HMOX1 protein concentrations . Plasma concentrations of OxLDL ( − 31.85 % , p < 0.001 ) , MCP-1 ( − 16.20 % , p = 0.020 ) and CRP ( − 7.32 % , p = 0.010 ) were decreased but MDA was not decreased ( 15.32 % , p = 0.107 ) . Within subjects , increment of plasma bilirubin concentration did not correlate with the changes in HMOX1 mRNA and protein concentrations , but correlated with low-density lipoprotein cholesterol decrement ( r = − 0.374 , p = 0.012 ) . Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers . Conclusion . Our prospect i ve observational trial finally confirms that atorvastatin ( 20 mg/day for 10 weeks ) increases plasma total bilirubin concentration . However , it seems that this effect is HMOX1-independent BACKGROUND Oxidative stress contributes to endothelial dysfunction , an important step to the pathogenesis of atherosclerosis and coronary events . Latest studies revealed the existence of pleiotropic and especially antioxidant properties of statins . We sought to examine the effects of pravastatin on lipid peroxidation and endothelial function , independently from lipid-lowering , in patients with unstable angina ( UA ) . METHODS Thirty-seven patients ( males ) , 64.46+/-9.09 years , suffering from UA enrolled in the study . Patients were not on statin medication before admission and they received after r and omization either 40 mg pravastatin daily ( group A , n = 20 ) , or placebo ( group B , n = 17 ) . Malondialdehyde ( MDA ) concentration , an index of lipid peroxidation and plaque instability , flow-mediated dilatation ( FMD ) of the brachial artery and blood lipids were measured on the second day of hospitalization and 10 days later . RESULTS MDA decreased significantly in both groups ( A , p = 0.008 ; B , p = 0.003 ) . FMD increased significantly in group A ( p = 0.007 ) , whereas in group B it did not change . Serum lipids remained unaltered in all three groups . CONCLUSIONS Pravastatin administration improved FMD within 10 days and this favorable effect occurred before any significant reduction in blood lipids , revealing its pleiotropic effects during the early phase of an acute coronary syndrome . Circulating lipid peroxidation products in patients with UA decreased significantly during the same period independently of endothelial function and pravastatin therapy A 12-month r and omized double blind controlled trial was conducted among 182 Indonesian postmenopausal women aged 47 to 60 years to determine the effect of 100 mg/day soy isoflavone supplementation on vascular endothelial function such as vascular cell adhesion molecule-1 ( VCAM-1 ) , nitric oxide ( NO ) and malondialdehyde ( MDA ) as oxidative stress marker . The subjects were r and omized to the intervention group receiving tablets consisting of 100 mg soy isoflavones and calcium carbonate 500 mg , and to the control group receiving 500 mg calcium carbonate . The concentrations of VCAM-1 , NO and MDA were measured at baseline , and postsupplementation at 6 months and 12 months . After supplementation , the MDA concentrations were significantly lower in the soy isoflavone group compared with the control group ( p=0.001 ) . The concentrations of VCAM-1 and NO were not affected ( p=0.992 and p=0.759 , respectively ) . In all group the MDA concentration increased compared with baseline concentrations but the relative change of MDA concentrations was significantly lower in the soy isoflavone group compared with the control group . This study demonstrates that supplemental intake of soy isoflavones for 6 months and 12 months had an effect on oxidative stress by decreasing MDA concentration , but did not improve vascular endothelial function OBJECTIVE Patients with systemic lupus erythematosus ( SLE ) experience excess morbidity and mortality due to coronary artery disease ( CAD ) that can not be fully explained by the classical CAD risk factors . Among emerging CAD risk factors , oxidative stress is currently being emphasized . We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE . METHODS Patients were r and omized to receive either placebo or vitamins ( 500 mg vitamin C and 800 IU vitamin E daily ) for 12 weeks . Markers of oxidative stress included malondialdehyde ( MDA ) and allantoin . Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase , plasma total antioxidant power ( as FRAP value ) , and ascorbic acid and vitamin E concentrations . Endothelial function was assessed by flow-mediated dilatation ( FMD ) of the brachial artery and plasma concentration of von Willebr and factor ( vWF ) and plasminogen activator inhibitor type 1 ( PAI-1 ) . Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels . Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function . RESULTS After treatment , plasma ascorbic acid and alpha-tocopherol concentrations were significantly ( p < 0.05 ) increased only in the vitamin-treated group , associated with a significant decrease ( p < 0.05 ) in plasma MDA . Other oxidative stress markers and antioxidant levels remained unchanged in both groups . FMD and vWF and PAI-1 levels remained unchanged in both groups . CONCLUSION Combined administration of vitamins C and E was associated with decreased lipid peroxidation , but did not affect endothelial function in patients with SLE after 3 months of therapy BACKGROUND Oxidative stress has been implicated in the development of endothelial damage in hemodialysis ( HD ) . We have assessed the effects of N-acetylcysteine ( NAC ) , a compound with antioxidant effects , on malondialdehyde ( MDA ) , a marker of oxidative stress on lipid peroxidation . METHODS A clinical trial was conducted in which 24 chronic HD patients were divided into 2 groups according to gender , age , time on HD and cause of renal failure . The NAC group ( n = 12 ) received 600 mg of NAC twice a day for 30 days . The remaining patients constituted the  control group  ( n = 12 ) . MDA levels were measured pre- and post-dialysis at the beginning of the study ( baseline ) and on day 30 ( 30 days ) . RESULTS Baseline pre- and post-dialysis MDA levels were not different between both groups and were above normal values . A significant decrease was found in the NAC group when either pre- or post-dialysis MDA levels were compared to the corresponding control group levels on day 30 ( pre-dialysis NAC vs control group 3.01 + /- 0.6 vs 4.5 + /- 0.73 micromol/l , p < 0.0001 , post-dialysis NAC vs control group 2.76 + /- 0.5 vs 4.39 + /- 0.7 micromol/l , p < 0.0001 ) . Only in the NAC group were pre-dialysis MDA 30-day levels different from pre-dialysis baseline levels ( 3.01 + /- 0.6 vs 5.07 + /- 1.6 micromol/l , p < 0.002 ) . Post-dialysis MDA 30-day concentrations were significantly lower than post-dialysis MDA baseline levels ( 2.76 + /- 0.5 vs 4.32 + /- 0.7 micromol/l , p < 0.002 ) and pre-dialysis MDA 30-day measurements ( 2.76 + /- 0.5 vs 3.01 + /- 0.6 micromol/l , p < 0.011 ) . CONCLUSIONS MDA levels are elevated in chronic HD patients and are not significantly reduced by HD . NAC significantly reduces malondialdehyde levels in chronic HD patients OBJECTIVE We investigated whether statin improves nitric oxide ( NO ) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes , compared with American Heart Association Step I Diet ( Diet ) . METHODS We administered diet+placebo and diet+simvastatin 20 mg daily during 14 weeks with r and omized order to 31 and 32 patients with coronary artery disease , respectively , with a r and omized design . RESULTS Compared with diet alone , simvastatin significantly improved the percent flow-mediated dilator response to hyperemia and lowered plasma levels of tumor necrosis factor (TNF)-alpha , intercellular adhesion molecule type-1 ( ICAM-1 ) , serum levels of CRP , and fibrinogen ( P<0.001 , P<0.001 , P=0.035 , P<0.001 and P=0.014 , respectively ) . Compared with diet alone , simvastatin lowered but statistically insignificant plasma levels of nitrate and malondialdehyde ( MDA ) ( P=0.164 and P=0.150 , respectively ) . Further , we observed that patients with the highest pretreatment TNF-alpha , ICAM-1 , and CRP levels showed the greatest extent of reductions on simvastatin . There were significant inverse correlation between low-density lipoprotein ( LDL ) cholesterol or the ratio of LDL to HDL cholesterol levels and flow-mediated dilation percent ( r=-0.342 , P=0.009 and r=-0.356 , P=0.006 , respectively ) . Of interest , there were significant inverse correlations between flow-mediated dilation percent and TNF-alpha levels ( r=-0.329 , P=0.010 ) . However , no significant correlations between lipoprotein levels and levels of inflammation markers were determined . Despite the significant changes of lipoproteins , diet alone did not decrease the markers of inflammation . CONCLUSIONS Compared with diet alone , simvastatin significantly reduced markers of inflammation more . These effects were independent of lipoprotein changes PURPOSE This study was design ed to ascertain the effects of a combination antioxidant therapy on plasma protein carbonyls ( PC ) , malondialdehyde ( MDA ) , and whole blood total ( TGSH ) , oxidized ( GSSG ) , and reduced ( GSH ) glutathione in non-resistance trained females after eccentric resistance exercise . METHODS Eighteen women ( aged 19 - 31 yr ) were r and omized in a double-blind manner to either an antioxidant supplement ( N = 9 ; 400 IU vitamin E , 1 g vitamin C , and 90 mug selenium per day ) or a lactose placebo ( N = 9 ) for 14 d before and for 2 d after eccentric elbow flexor exercise .  Blood sample s taken before and immediately , 2 , 6 , 24 , and 48 h postexercise were analyzed for PC , MDA , TGSH , and GSSG . RESULTS No treatment by time interaction was noted for any variable , with all blood markers experiencing a change after the exercise in both conditions . Time main effects were observed for PC , MDA , and GSSG , with values elevated above preexercise after the eccentric exercise , whereas GSH concentration decreased after the eccentric exercise . Antioxidant supplementation result ed in a condition main effect for PC and MDA , with lower values compared with placebo . The antioxidant treatment attenuated the rise in both PC ( 75 % ) and MDA ( 100 % ) . CONCLUSION These data suggest that eccentric resistance exercise can increase blood biomarkers of oxidative stress in non-resistance trained females , and this vitamin E , C , and selenium supplementation can attenuate the rise in PC and MDA Intravenous iron application to anemic patients on hemodialysis leads to an " oversaturation " of transferrin . As a result , non-transferrin-bound , redox-active iron might induce lipid peroxidation . To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III ) hydroxide sucrose complex intravenously during a hemodialysis session , 22 patients were investigated in a r and omized cross-over design , either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session . Blood was drawn before and 30 , 60 , 90 , 135 , and 180 min after the start of the iron infusion , and areas under the curve ( AUC0 - 180 min ) of ratios of plasma malondialdehyde ( MDA ) to cholesterol and plasma total peroxides to cholesterol ( two markers of lipid peroxidation ) were determined as the outcome variables . At baseline of the session without vitamin E supplementation , plasma alpha-tocopherol concentrations ( 27.6 + /- 1.8 micromol/L ) and ratios of alpha-tocopherol to cholesterol ( 5.88 + /- 1.09 mmol/mol ) were normal , plasma MDA concentrations were above normal ( 1.20 + /- 0.28 micromol/ L ) , and bleomycin-detectable iron ( BDI ) , indicating the presence of redox-active iron , was not detectable . Upon iron infusion , BDI and MDA concentrations increased significantly ( P < 0.001 ) . BDI concentrations explained the increase over baseline in MDA concentrations ( MDA = 1.29 + /- 0.075 x BDI ) . Vitamin E supplementation , leading to a 68 % increase in plasma alpha-tocopherol concentrations , significantly reduced the AUC0 - 180 min of MDA to cholesterol ( P = 0.004 ) and peroxides to cholesterol ( P = 0.002 ) . These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron .  Given that intravenous iron is applied repeatedly to patients on hemodialysis , this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term The aim of this placebo-controlled study was to investigate the effects of oral vitamin E supplementation for 10 weeks on exercise-induced oxidative damage in untrained dogs . Eight dogs were r and omly assigned to a  supplementation ( n=4 ) or control  ( n=4 ) group and underwent two isolated submaximal exercise sessions , 10 weeks apart . Blood was collected during each session to measure erythrocyte membrane fluidity ( EMF ) , paraoxonase-1 ( PON1 ) activity , plasma malondialdehyde ( MDA ) and vitamin E concentrations . These biomarkers were measured in venous blood sample s collected before ( t(0 ) ) , just after ( t , EMF only ) and 1d ( t+1d ) and 7d ( t+7d ) after the dogs ran on a treadmill . Prior to vitamin E supplementation , exercise induced a significant decrease in PON1 activity , EMF , vitamin E concentration and a significant increase in MDA concentration at t+1d . After a 10 week vitamin E supplementation period , these exercise-induced changes in PON1 activity , EMF and MDA concentration were still significant in the control group , but not in the supplemented group . These results suggested that vitamin E supplementation had a protective effect on submaximal exercise-induced oxidative damage in sedentary dogs Numerous studies have reported beneficial effects of antioxidant drugs on semen quality , but there is no well-defined therapeutical protocol in male infertility . This study aim ed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters . The study included 54 voluntary and infertile men who produced semen sample s for spermiogram and for spectrophotometric measurement of a lipid peroxidatio n marker , the malondialdehyde ( MDA ) , and produced blood sample s for high-perf ormance liquid chromatography assessment of serum vitamin E level . The trial was r and omized and open . Twenty-eight men were supplemented daily by vitamin E ( 400 mg ) and selenium ( 225 µg ) , during 3 months . The remaining 26 patients received vitamin B ( 4,5 g/day ) for the same duration . Only 20 patients achieved their treatment and returned for control analysis . MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels . In contrast to vitamin B supplementation , vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility . The results confirm the protective and beneficial effects of vitamin E and selenium  on semen quality and advocate their use in male infertility treatment Lipid-lowering therapy has been reported to reduce several oxidative stress ( OS ) markers in hypercholesterolemia . Since OS is frequently associated with renal dysfunction , we aim ed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine ( Tau ) , a sulfur amino acid with a marked antioxidant effect , in chronic kidney disease ( CKD ) . We enrolled 30 CKD r and omized to receive three different hypolipidemic regimens for 12 months : simvastatin alone ( 40 mg/day ) or ezetimibe/simvastatin combined therapy ( 10/20 or 10/40 mg/day ) .  Low molecular weight ( LMW ) thiols including homocysteine , cysteine , cysteinylglycine , glutathione , and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde ( MDA ) and allantoin/uric acid ( All/UA ) ratio were also evaluated . Tau concentration significantly increased throughout the therapy . The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day ( + 31.6 % after 1 year of therapy ) . A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients ( −19 % for both MDA and All/UA ratio ) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day ( −26 % for MDA and −28 % for All/UA ratio ) . Besides , an increase of thiols reduced forms was found ( + 20.7 % of LMW thiols redox status ) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day ( + 24.7 % ) . Moreover , we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels . We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level BACKGROUND  Asymmetric dimethylarginine ( ADMA ) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis ( HD ) patients . In the present study , we compared the effects of a vitamin E-coated polysulfone membrane ( PSE ) and a non-vitamin E-coated polysulfone membrane ( PS ) on oxidative stress markers such as ADMA . METHODS Thirty-one HD patients were enrolled to this investigation . They were allocated into two groups : in the PSE group ( n = 16 ) , PSE was used for 6 months , followed by PS for an additional 12 months ; in the PS group ( n = 15 ) , PS was used for the entire observation period . Plasma ADMA , oxidized low density lipoprotein ( Ox-LDL ) and malondialdehyde LDL ( MDA-LDL ) levels were measured at baseline , 3 , 6 , 12 and 18 months . Plasma ADMA in peritoneal dialysis ( PD ) patients and in healthy individuals was also measured . RESULTS Predialysis concentrations of ADMA ( 0.72+/- 0.13 nmol/ml ) were significantly higher in the HD group than in both PD patients ( 0.63+/-0.10 nmol/ml , P<0.01 ) and healthy individuals ( 0.44+/-0.01 nmol/ml , P<0.0001 ) . Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA ( 0.54+/-0.09 nmol/ml ) compared with baseline ( 0.74+/-0.12 nmol/ml ; P<0.01 ) . Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values . Treatment with PS subsequent to treatment with PSE again increased ADMA , Ox-LDL and MDA-LDL back to baseline levels . In the PS group , ADMA , Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months . CONCLUSIONS We confirmed that use of PSE reduced ADMA that had accumulated in HD patients . This finding indicates that PSE exerts anti-oxidant activity . A r and omized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress BACKGROUND Intravenous iron is widely prescribed in patients with chronic kidney disease ( CKD ) and can cause oxidative stress . The relationship of oxidative stress and renal injury in patients with CKD is unknown . Whether renal injury can occur at a time point when transferrin is incompletely saturated is also unclear . METHODS We conducted a r and omized , open-label , parallel group trial to compare the oxidative stress induced by intravenous administration of 100 mg iron sucrose over 5 minutes and its protection with N-acetylcysteine ( NAC ) in 20 subjects with stage 3 or 4 CKD . Transferrin saturation was measured with urea polyacrylamide gel electrophoresis , oxidative stress by malondialdehyde ( MDA ) measurement by high-performance liquid chromatography , and renal injury by enzymuria and proteinuria . Reduced and oxidized glutathione and free radical scavengers as well as urinary monocyte chemoattractant protein-1 were also measured . RESULTS Parenteral iron increased plasma concentration and urinary excretion rate of MDA , a biomarker of lipid peroxidation , within 15 to 30 minutes of iron sucrose administration . This was accompanied by enzymuria and increase in proteinuria . In contrast , saturation of transferrin was not maximally seen until 3 hours after the end of infusion . Oxidative stress , enzymuria and proteinuria were transient and were completely resolved in 24 hours . NAC reduced acute generation of systemic oxidative stress but failed to abrogate proteinuria or enzymuria . CONCLUSION Intravenous iron produces oxidative stress that is associated with transient proteinuria and tubular damage . The rapid production of oxidative stress even when transferrin is not completely saturation suggests free iron independent mechanism(s ) to be operative in producing oxidative stress and transient renal injury . Long-term implication s of these findings need further study Background — Statins improve clinical outcome of patients with atherosclerosis , but their perioperative role in patients undergoing coronary artery bypass grafting ( CABG ) is unclear . We hypothesized that short-term treatment with atorvastatin before CABG would improve the redox state in saphenous vein grafts ( SVGs ) , independently of low-density lipoprotein cholesterol (LDL)-lowering . Methods and Results — In a r and omized , double-blind controlled trial , 42 statin-naïve patients undergoing elective CABG received atorvastatin 40 mg/d or placebo for 3 days before surgery . Circulating inflammatory markers and malondialdehyde ( MDA ) were measured before and after treatment . SVG segments were used to determine vascular superoxide ( O2·− ) and Rac1 activation . For ex vivo studies , SVG segments from 24 patients were incubated for 6 hours with atorvastatin 0 , 5 , or 50 & mgr;mol/L. Oral atorvastatin  reduced vascular basal and NADPH-stimulated O2·− in SVGs ( P<0.05 for all versus placebo ) and reduced plasma MDA ( P<0.05 ) , independently of LDL-lowering and of changes in inflammatory markers . In SVGs exposed to atorvastatin ex vivo , without exposure to LDL , basal and NADPH-stimulated O2·− were significantly reduced ( P<0.01 for both concentrations versus 0 & mgr;mol/L ) in association with a striking reduction in Rac1 activation and 1 membrane-bound Rac1 and p67phox subunit . The antioxidant effects of atorvastatin were reversed by mevalonate , implying a dependence on vascular HMG-CoA reductase inhibition . Conclusions — Short-term treatment with atorvastatin 40 mg/d before CABG improves redox state in SVGs , by inhibiting vascular Rac1-mediated activation of NADPH-oxidase . These novel findings suggest that statin therapy should be maintained or initiated in patients undergoing CABG , independently of LDL levels . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01013103 Abstract . Purpose : We conducted a prospect i ve study to evaluate the effect of CO2 pneumoperitoneum and increased intra-abdominal pressure on arterial blood gases , end-tidal CO2 ( ETCO2 ) , nitric oxide ( NO ) , blood and tissue malondialdehyde ( MDA ) , and total antioxidant ( TAOx ) levels during laparoscopic cholecystectomy . Methods : Fifty selected patients with cholelithiasis were r and omized to undergo either laparoscopic or open surgery .  Blood sample s were taken pre- , mid- , and postinsufflation , and 24 h postoperatively . To determine the tissue MDA level , tissue sample s were taken from the gallbladder just after removal . Results : The increased levels of ETCO2 and PCO2 , caused by CO2 pneumoperitoneum result ed in a minimal decrease in blood pH during the laparoscopic surgery . Although low levels of blood MDA were seen 30 min after the start of laparoscopy , due to less oxidative stress response and tissue trauma , increased levels of tissue MDA levels indicated that the gallbladder was more traumatized during laparoscopic dissection and h and ling . NO levels were slightly lower in the laparoscopic cholecystectomy ( LC ) group , but there were no significant differences compared with the open cholecystectomy group ( OC ) . TAOx levels were similar in both groups 30 min after the start the procedure , but were much lower in the LC group 24 h postoperatively . Conclusions : These findings suggest that the antioxidant defense system is stimulated less with less oxidative stress , providing further evidence to support the opinion that LC is a safe technique Purpose The aim of this study was to investigate the effects of flaxseed oil consumption on serum systemic and vascular inflammation markers , and oxidative stress in hemodialysis ( HD ) patients . Methods In this r and omized , double-blind , clinical trial , 34 HD patients were r and omly assigned to either the flaxseed oil or the control group . The patients in the flaxseed oil group received 6 g/day flaxseed oil for 8 week , whereas the control group received 6 g/day medium-chain triglycerides ( MCT ) oil . At baseline and the end of week 8 , serum concentrations of high-sensitive C-reactive protein ( hs-CRP ) , soluble intercellular adhesion molecule type 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule type 1 ( sVCAM-1 ) , sE-selectin , and malondialdehyde ( MDA ) were measured after a 12- to 14-h fast . Results Serum hs-CRP , a systemic inflammation marker , and sVCAM-1 , a vascular inflammation marker , reduced significantly in the flaxseed oil group at the end of week 8 compared to baseline ( P < 0.05 ) , and the reductions were significant in comparison with the MCT oil group ( P < 0.05 ) . There were no significant differences between the two groups in mean changes in serum sICAM-1 , sE-selectin , and MDA . Conclusion This study indicates that daily consumption of 6 g flaxseed oil reduces serum hs-CRP and sVCAM-1 , which are two risk factors for CVD . Therefore , the inclusion of flaxseed oil in the usual diet of HD patients can be considered as a strategy for reducing CVD risk factors Summary Recent evidence suggests that the oxidative stress is an important factor in the pathophysiology of pre-eclampsia . The purpose of this study was to evaluate the possible relationship between increased resistance at the Doppler assessment of the uterine arteries between 20–23 gestational weeks and biochemical markers of oxidative stress , with the development of pre-eclampsia and /or growth restricted infants . This was a prospect i ve study of 34 pregnant women with normal uteroplacental flow and 30 women with abnormal uterine arteries Doppler analysis ( mean PI ≥ 1.60 ) during the transvaginal assessment of the uterine arteries at the routine anomaly scan . Blood sample s were obtained in order to assess the plasma oxidative stress , namely malondialdehyde ( MDA ) and uric acid levels . The MDA was significantly higher in the group of women with abnormal uterine arteries Dopplers . This group is at increased risk for the development of pre-eclampsia . The uric acid levels did not differ significantly between the two groups of women . There was no significant difference regarding the sensitivity or the specificity of the  uterine arteries Doppler examination in detecting pre-eclampsia in comparison to the combination of oxidative stress and Doppler 's . Our study provides additional evidence regarding the role of oxidative stress in the pathophysiology of pre-eclampsia . Whether antioxidant supplementation in the group of women with abnormal uterine Doppler 's is effective in reducing the incidence of the disease remains to be established Background Atorvastatin , an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase , which is used for lipid-lowering therapy , is an effective statin modulating process involved in atherosclerosis . Paraoxonase ( PON ) associated with high-density lipoprotein ( HDL ) has been postulated to have a role in protecting low-density lipoprotein ( LDL ) against oxidative modification . Oxidation of serum LDL is an important early step in the development of atherosclerosis and auto-antibodies against oxidized LDL ( AuAb-oxLDL ) reflect in-vivo LDL oxidation . Design and methods To examine the effect of atorvastatin ( 10 mg/day ) therapy on PON activity in serum and HDL , the study group included 40 patients with dyslipidemia ( 19 women and 21 men ) , 25 of whom had hypercholesterolemia and of 15 of whom had mixed-type hyperlipidemia . By taking blood sample s from the patients , levels of serum lipids , lipid peroxidation product as malondialdehyde ( MDA ) , total antioxidant status ( TAS ) and AuAb-oxLDL and the activities of PON in serum and isolated HDL were determined . Results The mean levels of total cholesterol , triglyceride , LDL-cholesterol , MDA and AuAb-oxLDL were decreased while HDL-cholesterol and TAS were increased significantly after lipid-lowering therapy in patients with dyslipidemia . On the other h and , PON activities in serum and HDL were increased significantly . The percentage increase in serum PON activity was associated significantly with the percentage decrease in serum AuAb-oxLDL ( r=−0.32 , P=0.047 ) and that of HDL PON activity was associated with the percentage increase in HDL-cholesterol level after atorvastatin therapy ( r=0.52 , P=0.001 ) . The therapy was more effective in increasing PON activity in patients with HDL levels above 35 mg/dl . Conclusion It was concluded that atorvastatin therapy in dyslipidemic patients decreases the level of oxidative stress and increases PON activity , especially in patients with HDL levels above 35 mg/dl The objective of this study was to investigate temperature dependent effects of oral l-carnitine supplementation on exhaustive exercise induced oxidative damage in rats . 42 male Spraque Dawley rats were r and omly divided into seven experimental groups . These groups were formed as three non-carnitine exercise groups , three carnitine-exercise groups and a sedentary group . l-carnitine was given intraperitoneally to the carnitine-exercise groups 1h before the exercise in 100mg/kg . Blood was collected to measure paraoxonase-1 ( PON1 ) activity , plasma malondialdehyde ( MDA ) , low-density lipoprotein ( LDL ) and cholesterol concentrations . These biomarkers were measured in venous blood sample s collected before and after the rats swam in pools at different water temperatures ( 18 ° C , 28 ° C and 38 ° C ) . In the non-carnitine group , exercise caused a significant decrease in PON1 activity and a significant elevation in MDA concentration at 28 ° C compared to the sedentary group . No significant alterations were evidence d in LDL and cholesterol concentrations upon exercise . The decrease in PON1 activity became higher with increasing temperature whereas the elevation in MDA levels increased at 18 ° C . In the l-carnitine supplementation group , recovery in PON1 activity was observed significant at 28 ° C and very significant at 38 ° C . MDA concentration was almost the same with that of the non-carnitine group at 18 and 38 ° C , but it significantly decreased at 28 ° C . Considering the recovery in PON1 and MDA levels at 28 ° C , which is the temperature of the sedentary group ; our results suggest that l-carnitine supplementation has a protective role on exhaustive exercise-induced oxidative stress . Findings of this study also demonstrate influences of thermal stress on these parameters during exhaustive exercise Oxidative stress has been related to ageing and risk of death . To determine whether oxidative status was associated with all-cause risk of death we carried out a prospect i ve study in 154 non-smoking Spanish elderly without major illness .  Baseline glutathione peroxidase ( GPx ) and superoxide dismutase ( SOD ) were analysed in plasma and erythrocytes . α-tocopherol , β-carotene , lycopene and retinol were determined in serum sample s and malondialdehyde ( MDA ) , as a lipid peroxidation marker , in plasma . Mean survival time was 4.3 years . A total of 31 death cases ( 20.1 % ) occurred during the follow-up . Plasma-MDA predicted mortality independently of all other variables , while erythrocyte-SOD ( e-SOD ) , β-carotene and α-tocopherol were positively associated with survival . α-tocopherol and MDA were revealed as independent predictors in a joint survival model , being the group with low MDA and high α-tocopherol that with the lowest mortality . In conclusion , a higher risk of death was associated with increased lipid peroxidation and lower antioxidant defenses Systemic sclerosis ( SSc ) has the highest case-specific mortality among the rheumatic diseases . Vascular dysfunction and structural wall abnormalities are among the earliest and fundamental alterations in SSc . Statins have a number of immunomodulating effects on vascular wall cells , which may modify the progression of vascular injury . The aim of this study was to evaluate the potential efficacy of statin therapy in ameliorating endothelial dysfunction ( ED ) in SSc by investigating the effect of statins on some markers that reflect endothelial activation in SSc . Forty patients with SSc were r and omized into two groups to receive 6 months ' treatment with atorvastatin ( n = 20 ; dose , 40 mg/day ) or placebo ( n = 20 ) as an adjuvant to existing therapy . Markers of ED including ET-1 , plasma nitrate levels , and thrombomodulin ( TM ) were evaluated by the enzyme-linked immunosorbent assay ( ELISA ) technique . Fibrinogen , high-sensitivity C-reactive protein ( hsCRP ) , ESR , lipid peroxide ( LP ) , and malonylaldehyde ( MDA ) levels were also assessed . Brachial flow-mediated vasodilatation was assessed by ultrasonography . Patients were studied at base line and after 6 months of statin therapy . After 6 months of therapy , ET-1 , ICAM-1 , sE-selectin , vWF , fibrinogen , ESR , hsCRP as well as LP and MDA levels declined and NO increased significantly in the statin-treated SSc group when compared to the placebo-treated group . Endothelium-dependent vasodilatation ( EDV ) improved significantly in the atorvastatin-treated group . The findings of this study demonstrated statin-mediated improvements in the endothelial function of SSc patients as well as immunomodulating effects . Statins may thus prove to be an invaluable addition to the therapy of the vasculopathy of SSc Background : During  conventional cardiac surgery  ischemia and reperfusion may cause excessive production of reactive oxygen species leading to tissue damage including early arrhythmias . We therefore assessed the kinetics of markers of radical stress including oxidized and reduced glutathione ( GSSG/GSH ) , oxidized proteins ( PCG ) and malondialdehyde ( MDA ) , and tested the hypothesis that different steroid treatments inhibit these markers and early reperfusion‐associated supraventricular and ventricular extrasystolic beats PURPOSE Aging is associated with increased oxidative stress , whereas systematic exercise training has been shown to improve quality of life and functional performance of the aged . This study aim ed to evaluate responses of selected markers of oxidative stress and antioxidant status in inactive older men during endurance training and detraining . METHODS Nineteen older men ( 65 - 78 yr ) were r and omly assigned into either a control ( C , N = 8) or an endurance-training ( ET , N = 11 , three training sessions per week , 16 wk , walking/jogging at 50 - 80 % of HR(max ) ) group . Before , immediately posttraining , and after 4 months of detraining , subjects performed a progressive diagnostic treadmill test to exhaustion ( GXT ) . Plasma sample s , collected before and immediately post-GXT , were analyzed for malondialdehyde ( MDA ) and 3-nitrotyrosine ( 3-NT ) levels , total antioxidant capacity ( TAC ) , and glutathione peroxidase activity ( GPX ) . RESULTS ET caused a 40 % increase in running time and a 20 % increase in maximal oxygen consumption ( VO(2max ) ) ( P < 0.05 ) . ET  lowered MDA ( 9 % at rest , P < 0.01 ; and 16 % postexercise , P < 0.05 ) and 3-NT levels ( 20 % postexercise , P < 0.05 ) , whereas it increased TAC ( 6 % at rest , P < 0.01 ; and 14 % postexercise , P < 0.05 ) and GPX ( 12 % postexercise , P < 0.05 ) . However , detraining abolished these adaptations . CONCLUSIONS ET may attenuate basal and exercise-induced lipid peroxidation and increase protection against oxidative stress by increasing TAC and GPX activity . However , training cessation may reverse these training-induced adaptations Type 2 diabetes ( T2D ) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products . Since reactive oxygen species ( ROS ) can cause damage to biological macromolecules including DNA , this study investigated oxidative damage to DNA using the alkaline ( pH > 13 ) comet assay in peripheral whole blood leukocytes sample d from 15 dyslipidemic T2D patients treated with simvastatin ( 20 mg/day ) , 15 dyslipidemic T2D patients not treated with simvastatin , 20 non‐dyslipidemic T2D patients , and 20 healthy individuals ( controls ) . Our results showed a greater DNA migration in terms of damage index ( DI ) ( p < 0.01 ) in the dyslipidemic T2D patients not treated with statin ( DI = 67.70 ± 10.89 ) when compared to the dyslipidemic T2D patients under statin treatment ( DI = 47.56 ± 7.02 ) , non‐dyslipidemic T2D patients ( DI = 52.25 ± 9.14 ) , and controls ( DI = 13.20 ± 6.40 ) . Plasma malondialdehyde ( MDA ) and C‐reactive protein ( CRP ) levels were also increased and total antioxidant reactivity ( TAR ) and paraoxonase activity ( PON1 ) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin . We also found that DI was inversely correlated with TAR ( r = −0.61 , p < 0.05 ) and PON1 ( r = −0.67 , p < 0.01 ) . In addition , there was a significant positive correlation between DI and CRP ( r = 0.80 , p < 0.01 ) . Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients . Copyright © 2010 John Wiley & Sons , Background : Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products ( AGEs ) . Curcumin can reduce the accumulation of AGEs in vitro and in animal models . We examined whether supplementation with curcumin and Boswellia serrata ( BSE ) gum resin for 3 months could affect plasma levels of markers of oxidative stress , inflammation , and glycation in healthy master cyclists . Methods . Forty-seven healthy male athletes were r and omly assigned to Group 1 , consisting of 22 subjects given a Mediterranean diet ( MD ) alone ( MD group ) , and Group 2 consisted of 25 subjects given a MD plus curcumin and BSE ( curcumin/BSE group ) . Interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNFα ) , high-sensitivity c-reactive protein ( hs-CRP ) , total AGE , soluble receptor for AGE ( sRAGE ) , malondialdehyde ( MDA ) , plasma phospholipid fatty acid ( PPFA ) composition , and non-esterified fatty acids ( NEFA ) were tested at baseline and after 12 weeks . Results : sRAGE , NEFA , and MDA decreased significantly in both groups , while only the curcumin/BSE group showed a significant decline in total AGE . Only the changes in total AGE and MDA differed significantly between the curcumin/BSE and MD groups . Conclusions . Our data suggest a positive effect of supplementation with curcumin and BSE on glycoxidation and lipid peroxidation in chronically exercising master athletes BACKGROUND Patients with end-stage renal failure undergoing haemodialysis ( HD )  are exposed to oxidative stress . Increased levels of malondialdehyde ( MDA ) were demonstrated in plasma of uraemic patients , indicating accelerated lipid peroxidation ( LPO ) as a consequence of multiple pathogenetic factors . The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients . METHODS MDA and  4-hydroxynonenal ( HNE ) were measured in three groups of patients undergoing HD : group I comprised eight patients with a blood haemoglobin ( Hb ) < 10 g/dl ( mean Hb = 8.1+/-1.3 g/dl ) , and group II were eight patients with a Hb > 10 g/dl ( mean Hb=12.4+/-1.9g/dl ) ; none of these 16 patients had been treated with human recombinant erythropoietin ( rHuEpo ) . Group III comprised 27 patients with a mean Hb of 10.5+/-1.6 g/dl after long-term rHuEpo treatment . RESULTS Mean plasma concentrations of both MDA and HNE were significantly higher ( P<0.0001 ) in all 43 HD patients than in 20 healthy controls ( MDA 2.85+/-0.25 vs 0.37+/-0.03 microM , HNE 0.32+/-0.03 vs 0.10+/-0.01 microM ) . Comparing the three groups , it was shown that HD patients with a Hb < 10 g/dl had significantly higher plasma levels of LPO products ( MDA 3.81+/-0.86 microM , HNE 0.45+/-0.07 microM ) than HD patients with a Hb > 10g/dl ( MDA 2.77+/-0.58 UM , HNE 0.25+/-0.05 microM ) , and than HD patients treated with rHuEpo ( MDA 2.50+/-0.12 microM , HNE 0.29+/-0.03 microM ) . Furthermore , an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen ( r=0.62 , P<0.0001 ) . CONCLUSION Radical generation in HD patients might be caused in part by renal anemia itself . Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration
Conclusions : This systematic review and meta- analysis showed that statin treatment significantly reduces systemic MDA concentrations .
Background : The effect of statins on oxidative stress markers , such as malondialdehyde ( MDA ) , is still a matter of debate .
We sought to address this issue by conducting a systematic review and meta- analysis of published data on the effect of statin treatment on systemic MDA concentrations .