不同吸入浓度的七氟烷对大鼠体内组织氧化和抗氧化作用的影响

目的挥发性麻醉药可引起缺血再灌注损伤,且与氧化应激及炎症的发生相关,部分可能会加重氧化应激,部分表现出抗氧化作用。本实验为评估大鼠暴露于不同浓度的七氟烷中,肝、脑、肾、肺组织氧化应激程度。方法将实验动物分为3组:对照组(只接受空气)、高浓度七氟烷(7%)和低浓度七氟烷(2%)。经过4 h的暴露,评估大鼠相应组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、铜(Cu)、锌(Zn)的指标。结果暴露于不同浓度的七氟烷中大鼠肺组织MDA水平均较对照组明显增加,而不同浓度的七氟烷在其他组织氧化应激中和抗氧化活性表现均不同。结论高低浓度的七氟烷在体内实验中均具有抗氧化及抑制氧化应激的作用,但肺部的氧化损伤最重。     

格雷夫斯病患者体内抗氧化状态及氧化损伤的研究

目的:观察格雷夫斯病(GD)患者体内抗氧化状态及生物大分子的氧化损伤情况。方法: 检测GD初发组和治疗组各31例患者血浆总抗氧化能力(TAC)、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性及血浆丙二醛(MDA)和巯基(SH)含量,与31例正常对照比较;采用单细胞凝胶电泳法(SCGE)检测各组外周血单个核细胞(PBMC)的DNA损伤情况(用彗星率表示)。结果: GD初发组血浆TAC、SOD、GSH-Px活性及SH含量明显低于对照组(P＜0.05,P＜0.01),MDA含量及彗星率明显高于对照组(P＜0.01);GD治疗组各指标明显轻于初发组(P＜0.05,P＜0.01),但仍未达到对照水平。GD初发组及治疗组患者PBMC彗星率与TAC呈负相关,与MDA含量呈正相关。 结论:GD患者体内存在氧化应激及脂质、蛋白质和DNA的氧化损伤,生物大分子的氧化损伤可能参与GD的发生和发展。     

急性脑卒中患者血清氧化应激指标测定及临床意义

目的:分析急性脑卒中患者氧化应激指标水平变化及其临床意义。方法:采用生物化学方法检测90例急性脑卒中患者(病例组)和50例健康体检者(对照组)血清超氧化物歧化酶(SOD)、丙二醛(MDA)水平和总抗氧化能力(T-AOC),并将病例组进一步分为脑出血组和脑梗死组,比较两组氧化应激指标的差异。结果:病例组血清SOD和T-AOC水平明显降低,MDA水平明显升高,差异均有统计学意义(P<0.05)。与脑梗死组相比,脑出血组血清SOD水平显著降低(P<0.05),MDA水平明显升高(P<0.05),T-AOC水平变化无明显差异(P>0.05)。结论:急性脑卒中患者抗氧化能力明显降低,氧化损伤作用增强。     

大鼠体外循环后血浆二胺氧化酶活性变化与肠屏障损伤的关系

目的：观察探讨体外循环（CPB）过程中大鼠血浆二胺氧化酶（DAO）活性变化规律及其与肠损伤指标变化的关系。 方法： 建立大鼠体外循环模型，按时点采血测定血浆DAO活性和D-乳酸、脂多糖(LPS)的浓度并进行统计分析。 结果： CPB后血浆DAO活性呈现双峰升高，第1峰值在CPB转流结束后即刻，时相上早于血浆LPS和D-乳酸的升高；第2峰值在CPB结束后3 h，在肠损伤指标变化峰值之后。 结论： CPB过程中肠粘膜屏障受到缺血和再灌注二次损伤的打击，血浆DAO活性作为反映肠损伤的指标特异性强，灵敏度高，对CPB术后病情判断和并发症防治提供参考。     

2型糖尿病微血管病变患者血浆对氧磷酯酶-1活性与氧化应激的关系

目的探讨2型糖尿病微血管病变(DMPA)患者血浆对氧磷酯酶-1(PON-1)活性与氧化应激的关系。方法168例2型糖尿病根据微血管并发症情况分为无微血管并发症(NDC)组、糖尿病视网膜病变(DR)组和糖尿病肾病(DN)组,分别检测各组患者血浆PON-1、超氧化物歧化酶(SOD)和循环谷胱甘肽过氧化物酶(GSHPx)活性、丙二醛(MDA)含量,分析PON-1活性与SOD、MDA、GSHPx之间的关系。结果糖尿病各组患者血浆PON-1、SOD、GSHPx活性均明显低于对照组(P<0.01),DMPA组又低于NDC组(P<0.05),而血浆MDA含量与对照组比较显著升高(P<0.01),DMPA组又高于NDC组(P<0.05)。相关分析表明,糖尿病患者血浆PON-1活性与GSHPx、SOD呈正相关(r=0.774,P<0.01;r=0.801,P<0.01),与MDA呈负相关(r=-0.833,P<0.01)。结论在2型糖尿病DMPA中氧化应激增强及血浆PON-1活性显著降低,PON-1与氧化应激及其相互作用参与了2型糖尿病DM-PA的发生和发展。     

PTEN、FOXO3a和氧化应激相关蛋白在胃癌组织中的表达

目的:探讨PTEN、FOXO3a和氧化应激相关蛋白在胃癌中的表达及它们之间的相互关系。方法:采用紫外分光光度法测定胃腺癌患者(n=45)和健康自愿者(n=30)血浆中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)及丙二醛(MDA)的表达水平;采用荧光定量RT-PCR法检测胃腺癌组织(n=84)和正常组织(n=48)中PTEN mRNA和FOXO3a mRNA的表达水平。PTEN和FOXO3a的表达与氧化应激的关系采用Spearman方法进行相关性分析。结果:胃癌组血浆中CAT、SOD表达低于对照组,MDA表达高于对照组;胃癌组织中PTEN mRNA和FOXO3a mRNA表达低于正常组织;PTENmRNA表达与SOD、CAT的含量呈正相关,与MDA的含量呈反相关。结论:胃腺癌患者体内存在过高的氧化应激水平及过低的抗氧化水平,机体抗氧化能力的降低有可能降低抑癌基因PTEN mRNA和FOXO3a mRNA的表达。     

过氧化物酶Ⅰ、过氧化氢酶、超氧化物歧化酶在大鼠肝缺血再灌注损伤小肠内的表达变化

目的:观察过氧化物酶Ⅰ(PrxI)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)在大鼠肝缺血再灌注损伤模型小肠内的表达变化以及小肠内氧化应激的水平,探讨肝缺血再灌注损伤对小肠的影响及PrxI、CAT、SOD的抗氧化作用。方法:制备大鼠70%肝缺血再灌注损伤模型。肝缺血再灌注6h后取血、肝和小肠。采用全自动生化分析仪测定血清丙氨酸氨基转移酶(ALT)活性;钼酸比色法和硫代巴比妥酸比色法测定血清、小肠中H_2O_2和丙二醛(MDA)的含量;H-E染色法观察肝、小肠的形态学改变;RT-PCR测定小肠组织PrxI、CAT、SOD mRNA水平的表达,免疫印迹测定其蛋白水平的表达。结果:与对照组相比,肝缺血再灌注损伤组大鼠血清ALT活性、MDA和H_2O_2的含量明显升高;H-E染色结果显示模型组大鼠肝组织形态结构受损明显;小肠组织内MDA和H_2O_2的含量明显高于对照组,PrxI、CAT、SOD的mRNA和蛋白表达水平与对照组相比也升高明显。结论:PrxI、CAT和SOD在小肠组织处于高度氧化应激状态过程中可能发挥了抗氧化应激作用。     

动脉粥样硬化与血浆抗氧化活性

目的:探讨高胆固醇血症所致动脉粥样硬化(AS)发病过程中脂质过氧化激活机制。方法:选择健康雄性家兔，每天定量加胆固醇饲料(0.25 g/kg)饲养。时间 12周，每隔2周从兔耳取静脉血，测量血清铜蓝蛋白-转铁蛋白系统的抗氧化活性及血清胆固醇(Ch)和雨二醛(MDA)含量。结果:饲养12周后，部分兔血清钢蓝蛋白-转铁蛋白系统抗氧化活性明显增强，Ch含量增加 3倍，MDA含量明显下降。其余兔血清铜蓝蛋白-转铁蛋白系统抗氧化活性无明显变化，Ch含量增加 10倍，MDA含量显着提高。结论:高胆固醇血症所致AS的发生过程可能是多种脂质过氧化激活机制综合作用的结果，增强血浆抗氧化活性可在一定程度上抑制Ch和脂质过氧化物(LPO)积累，延缓AS的发生。     

氧化应激与诱导性一氧化氮合酶在糖尿病性阴茎勃起功能障碍中的作用

目的:探讨氧化应激与诱导性一氧化氮合酶(iNOS)在糖尿病性阳茎勃起功能障碍(ED)中的可能作用。方法:注射链脲佐菌素建立糖尿病大鼠模型,分别在注射8周和12周后观察阴茎勃起次数、取大鼠阴茎和血浆,测定血清丙二醛(MDA)水平、总抗氧化能力(T-AOC)、一氧化氮合酶(NOS)和iNOS活力以及用免疫组织化学ABC方法检测阴茎iNOS的表达。结果:糖尿病大鼠的阴茎勃起次数明显低于对照组,并随病程延长降低;糖尿病大鼠血清MDA、iNOS水平明显高于对照组;糖尿病大鼠T-AOC水平明显低于对照组;与对照组比较,糖尿病组阴茎内iNOS阳性细胞数和平均光密度值随病程延长而升高。结论:糖尿病性阴茎勃起功能障碍与氧化应激水平、血清iNOS活性以及阴茎iNOS的表达升高相关。     

老年糖尿病酮症酸中毒患者IL-6和氧化应激的变化

目的: 探讨老年糖尿病酮症酸中毒(DKA)患者白细胞介素6(IL-6)和氧化应激的变化.方法:检测老年糖尿病酮症酸中毒患者治疗前后血IL6、 8异前列腺素F-2α(8-isoprostaglandinF2α,8isoPGF2α)水平、超氧化物歧化酶(SOD）活性、总抗氧化能力(TAC)和丙二醛(MDA）含量.结果:在DKA患者SOD、 TAC显著低于对照组(P<0.05), 而IL6、 MDA和8isoPGF2α显著高于对照组(P<0.05); DKA患者治疗后的SOD和TAC显著高于治疗前患者(P<0.05), 而IL-6、 MDA和8isoPGF2α显著低于治疗前患者(P<0.05).DKA患者治疗前IL6与8isoPGF2α呈显著性正相关(r=0.33, P<0.05）, 治疗后IL-6与SOD呈显著性负相关(r=-0.36, P<0.05）.DKA患者治疗前后IL-6与MDA均呈显著性正相关(r=0.38, 0.41, P<0.05）.结论: DKA患者血清IL-6水平明显升高, 且与氧化应激有关.     

Anemia associated with extraerythrocytic oxidative stress damage mediated by neutrophil superoxide anion production in chronic renal failure patients undergoing hemodialysis

Anemia in patients with uremia undergoing hemodialysis (HD) is a complex process that is dependent on erythropoiesis associated with erythropoietin and iron availability. Published information about an extra erythrocytic factor in the data concerning HD and the underlying mechanism by which anemia occurs remain unclear. The aim of this study was to investigate the superoxide anion generation by polymorphonuclear neutrophils and red blood cell (RBC) lipid peroxidizability as well as the possible association between these parameters and anemia in patients undergoing HD. Blood was collected from 15 volunteers prior to and following HD, and hematological data showed significant anemia at both time points. RBC lipid peroxidizability and neutrophil anion superoxide production, as evaluated by kinetics analysis, revealed increased initial and maximal velocity before and after HD. Plasma malondialdehyde (MDA) and antioxidant levels in the patient group were higher than those in the control group. RBC superoxide dismutase and catalase activities did not differ between groups. There was a significant correlation between increased RBC lipid peroxidizability and superoxide anion production and anemia in patients undergoing HD. The individual variation in plasma MDA was accompanied by superoxide anion production. The RBC lipid peroxidizability, mediated by neutrophil-generated superoxide anions, seems to be a plausible mechanism for explaining, in part, the extraerythrocytic damage that leads to anemia in patients on HD.     

Antioxidant parameters and ageing in some animal species

Connection between ageing and some tissue antioxidant parameters have been studied in four experiments on different animal species. Prenatal studies on the developing chick embryos showed discrepancies between the lipid-rich liver and brain antioxidant defence. In the liver, high levels of reduced glutathione (GSH), vitamins A and E and high activities of the antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) were found whereas brain expressed a high vitamin C concentration. In newborn healthy calves during the first two days of life, atmospheric oxygen tension did not cause either increased lipid peroxidation as reflected in a high malondialdehyde (MDA) level or any changes in GSII, GPX, SOD and catalase (CAT) activities in red blood cells (RBC). Plasma vitamin E and carotene concentrations also did not change. In growing healthy calves during two months after birth increasing MDA, decreasing GSH, GPX and CAT are leading features, whereas plasma vitamin E and carotene concentrations significantly increased. In young (1-year-old) and old (9-year-old) dogs RBC results showed significant differences with the highest MDA and lowest GSH levels in the old males. Activity of GPX and SOD was higher in old dogs than in the young ones, especially in the females.     

Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.     

Ischemia of the intestinal mucosa during cardiopulmonary bypass

 Bacterial translocation is believed to occur during cardiopulmonary bypass (CPB) because serum endotoxin concentrations rise. Intestinal ischemia during CPB, however, has never been proven directly. The condition of the intestinal mucosa during CPB was studied by measuring serum diamine oxidase (DAO) activity, an index of intestinal ischemia. Serum DAO activity, blood lactate concentration, and the arterial ketone body ratio (AKBR) were measured intraoperatively in four successive patients who underwent aortic arch replacement by the open distal anastomosis method. DAO activity rose after restoration of blood flow to the lower half of the body, and continued to rise throughout CPB. The lactate concentration also rose, mirroring the change in DAO activity, and returned to nearly normal 12 h after the operation. The AKBR decreased during CPB, with a mean minimum vale of 0.16 ± 0.07 immediately after the restoration of blood flow to the lower half of the body. The parallel rise in DAO activity and serum lactate concentration once blood flow to the lower half of the body was restored implies that ischemic injury to the mucosa of the small intestine occurs during CPB. The continued rise in these parameters throughout CPB is consistent with ongoing injury due to splanchnic hypoperfusion, as reflected in the decrease in the AKBR during the same period. Received: October 18, 2002 / Accepted: February 20, 2003     

In vitro comparison of blood pump induced platelet microaggregates between a centrifugal and roller pump during cardiopulmonary bypass

Platelets are consumed during cardiopulmonary bypass (CPB) and mechanical ventricular assistance, at least partly as a result of the formation of platelet microaggregates in the blood pump. There is no commonly accepted method currently available to detect platelet microaggregates during the use of CPB or left ventricular assist devices (LVAD). The purpose of this study was to develop a flow cytometric method for the quantification of platelet microaggregates generated in blood pumps, and to evaluate the effect of cellular fragments from hemolyzed erythrocytes on the perioperative assessment of platelet counts during CPB. METHOD: Fresh human anticoagulated blood (1IU heparin/mL, activated clotting time 250+/-24 sec.) was circulated for 120 minutes in an artificial circulatory system, containing either a centrifugal pump (CP) or roller pump (RP). Whole blood was used to quantify platelet consumption and to detect circulating platelet microaggregates in a flow cytometer. Platelet consumption was additionally analyzed using an automated "Coulter" blood cell counter. Hemolysis was analyzed by measurement of plasma free hemoglobin (fHb), as well a by flow cytometric detection of red blood cell (RBC) fragments. RESULTS: Flow cytometric analysis demonstrated significantly more circulating platelet aggregates and platelet consumption in the RP than in the CP (p<0.01). Quantification of RBC fragments and plasma free hemoglobin (fHb) levels also indicated significantly increased hemolysis in the RP than in the CP (p<0.01). In contrast, the Coulter count data indicated less platelet consumption in the PP compared to the CP. CONCLUSION: Fragments from hemolyzed erythrocytes have the same size distribution as intact platelets and the number of RBC fragments correlates with the extent of pump-induced hemolysis during CPB. Our data suggest that assessment of platelets by "Coulter counting" cannot distinguish platelets from RBC fragments and may underestimate platelet consumption in the presence of hemolysis during CPB. We conclude that flow cytometry is more accurate in the perioperative assessment of platelet count and platelet aggregation during CPB and LVAD support.     

Lipid peroxidation, erythrocyte superoxide-dismutase activity and trace metals in young male footballers

Physical training is known to induce oxidative stress in individuals subjected to intense exercise. In this study, we investigated plasma malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) activity of 25 young male footballers and a control group of similar age. Red blood cell (RBC) count, haemoglobin (Hb) and haematocrit (Hct) values, and copper (Cu) and zinc (Zn) levels were also examined. The maximal oxygen uptake (VO2max) of all subjects was determined in order to establish their functional capacity. The main finding of the present study was that plasma MDA levels, one of the most commonly used markers of lipid peroxidation, of this group of footballers aged under 21 decreased slightly when compared with those of the control group (p < 0.001). In contrast, erythrocyte SOD activity was higher in the footballer group than in the controls (p < 0.001). Footballers who are under regular training showed an improved antioxidant activity in comparison to sedentary controls. Plasma copper concentration, RBC count and Hb concentration of the footballer group were all significantly lower than those of the control group, (p < 0.001, p < 0.01, p < 0.01, respectively). Investigating the footballers' data with Spearman's correlation analyses, the correlation coefficients (r) between Zn/Cu ratio and SOD was positive (r=0.44; p < 0.05); and between VO2max and SOD (r=0.42; p < 0.05) were both positive. On the basis of statistical analysis, we suggest that regular exercise may be beneficial in cases of oxidative damage by reducing the amount of lipid peroxidation and increasing the activity of the antioxidant enzyme SOD.     

Effect of magnesium supplementation on oxidative stress in alloxanic diabetic rats.

Magnesium deficit and oxidative stress are common features of the diabetic state. This concept supported by another observation that magnesium deficiency is also a state of increased oxidative stress prompted us to study the effect of magnesium supplementation on magnesium status and oxidative stress in diabetic rats. For this purpose, male Wistar rats were made diabetic with a single intraperitoneal injection of Alloxan. Experimental diabetes caused a significant decrease in serum and red blood cell magnesium levels and increased urinary excretion of magnesium. Marked increase in plasma malondialdehyde and corresponding decrease in vitamins C & E, uric acid and total thiols was observed in the diabetic rats as compared to control group. In liver, MDA levels were increased significantly with concomitant decrease in vitamin C, non-protein thiols and antioxidant enzymes (SOD & GST). Magnesium supplementation for four weeks restored serum and RBC magnesium levels to near normal levels with marginal but significant decrease in blood glucose levels. Plasma and liver MDA levels were reduced significantly and vitamin C and total thiols were increased significantly with magnesium supplementation. Antioxidant enzyme activity was also increased significantly with magnesium supplementation in diabetic rats. Our data clearly demonstrates that alloxanic diabetes is associated with decreased magnesium status and increased oxidative stress and that magnesium supplementation can in part restore the antioxidant parameters and decrease the oxidative stress in experimental diabetic rats.     

Physical activity, aerobic capacity and selected markers of oxidative stress and the anti-oxidant defence system in healthy active elderly men.

The relationship of oxidative stress and the anti-oxidant defence system to maximal oxygen consumption (VO2max) and habitual physical activity was assessed in 26 elderly men (71.0 +/- 4.2 years) and compared to that of 12 young men (22.1 +/- 5.1 years). Physical activity was assessed by a questionnaire. Malondialdehyde (MDA), plasma total anti-oxidant status (TAS), the levels of red blood cell (RBC) superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as serum GPX activities were determined under resting conditions. The older and young men had similar TAS and RBC SOD, while MDA, RBC GPX and plasma GPX were higher, and RBC SOD/GPX ratio was significantly lower in the older men. Neither MDA nor anti-oxidants were associated with any of the physical activity/aerobic capacity measures in the elderly men. We conclude that in healthy elderly men with a good nutritional status, indicators of the anti-oxidant defence system are not lower in comparison with young men. Increased RBC and plasma GPX coupled with a high level of lipid peroxidation marker may indicate an adaptation of anti-oxidant defences to sustained oxidative stress. Furthermore, the results of the present study suggest that the level of habitual physical activity and aerobic capacity have no major influence on the resting balance between radical generation and blood anti-oxidant potential in healthy older men.     

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Objective and design: Cardiopulmonary bypass (CPB) impairs monocyte and neutrophil proliferation, cytokine synthesis, and antigen presentation. This study compares in vivo data with results from an extracorporeal circulation (ECC) model, distinguishing direct effects on cytokine synthesis from regulatory mechanisms. Patients and methods: Whole blood from 18 patients prior to, during and after CPB was stimulated with lipopolysaccharide (LPS). Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels were measured. Additionally, blood from 4 volunteers was circulated in an ECC model. Cytokine levels were measured before and during mock ECC. Results: LPS-induced cytokine synthesis was reduced after CPB (TNF-α: 11 %; IL-6: 29 %; IL-8: 48 % of preoperative values, all p < 0.001). In mock ECC, cytokine production (except IL-8) was suppressed: TNF-α production was lowest 60 min after starting ECC, IL-6 synthesis was lowest at 90 min (33 % and 15 % vs. pre-ECC levels; both p < 0.001). Patient sera contained cytokine-inhibitory activity after CPB, an activity not found in mock ECC. Conclusions: (1) In patients, CPB induces early transient LPS hyporesponsiveness; (2) blood contact with foreign surfaces induces LPS hyporesponsiveness; (3) serum cytokineinhibitory activities are released after CPB, but not in mock ECC. Impaired leukocyte function may explain increased susceptibility to infections after CPB. Received 16 September 2006; accepted without revision by K. Visvanathan 18 October 2006     

Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro

OBJECTIVE: The oxidation of low-density lipoprotein (LDL) is an important factor in the development of atherosclerosis. The antioxidant activity of some compounds buffers the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Estrogens are potent antioxidants of LDL, in vitro and in vivo, a mechanism that could probably influence the cardioprotection associated with hormone replacement therapy in postmenopause. We conducted an in vitro study of the antioxidant effect on LDL of two selective estrogen receptor modulators, raloxifene (RLX) and tamoxifen (TMX), comparing them with the known antioxidant effect of estradiol (E2 ). DESIGN: LDL was isolated by ultracentrifugation from plasma obtained from 12 healthy, untreated, postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with CuSO4 (15 micro M) to induce oxidative stress and with one of the three compounds studied: RLX, TMX, or E2 at doses of 0, 1, 2, 3, 5, 15, 50, and 500 micro M, and 1 and 2 mM. Malonaldehyde (MDA, nmol/mg protein) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration. MDA values decreased significantly, as compared with baseline, starting at a concentration of 2 micro M for RLX and 3 micro M for both, TMX, or E2. The dose necessary to reduce the generation of MDA by 50% was significantly lower for RLX (3.3 micro M, < 0.001) than for E2 (24.6 micro M ) or TMX (35.3 micro M). The area under the curve also showed a higher antioxidant activity for RLX compared with TMX or E2 ( < 0.001). CONCLUSIONS: The in vitro antioxidant activity of RLX is substantially more potent than TMX or E2. This finding, added to the other beneficial effects of the drug in the cardiovascular system, could imply some cardioprotector effect.