银杏叶提取物对饲高胆固醇兔动脉粥样硬化和低密度脂蛋白体外氧化的作用

目的 :观察银杏叶提取物对饲高胆固醇兔动脉粥样硬化斑块形成和低密度脂蛋白体外氧化的拮抗作用。方法 :采用饲高胆固醇兔动脉粥样硬化模型 ,观察银杏叶提取物对兔主动脉动脉粥样硬化斑块形成的影响 ;采用铜离子 (10× 10 -6mol/L)体外氧化低密度脂蛋白模型 ,观察银杏叶提取物对低密度脂蛋白脂质过氧化产物丙二醛 (MDA)含量和维生素E水平的影响。结果 :银杏叶提取物 (0 5 g/kg/天 )明显减少饲高胆固醇兔主动脉动脉粥样硬化斑块面积百分比 (19 0 %± 8 2 %vs 44 9%±17 6 % ,P <0 0 1) ;银杏叶提取物明显抑制铜离子氧化低密度脂蛋白致MDA增加和维生素E减少 (P<0 0 5 ) ,且呈剂量依赖性和时间依赖性。结论 :银杏叶提取物有延缓饲高胆固醇兔动脉粥样硬化斑块形成的作用和抗低密度脂蛋白体外氧化修饰的作用。     

辛伐他汀的调脂及抗动脉粥样硬化作用

采用食饵性兔动脉粥样硬化为模型 ,以舒降之为阳性对照药 ,研究辛伐他汀的调脂及抗动脉粥样硬化作用。将 5 6只雄性新西兰兔 (体重 1.96± 0 .16kg)随机分为对照组 (颗粒饲料 12 0～ 15 0g d ,n =14 )、动脉粥样硬化模型组 [颗粒饲料 +胆固醇 0 .5g (kg·d) ,n =14 ]、舒降之组 [颗粒饲料 +胆固醇 +舒降之片 5mg (kg·d) ,n =14 ]和辛伐他汀组 [颗粒饲料 +胆固醇 +辛伐他汀片 5mg (kg·d) ,n =14 ]。在实验前、实验第 8、12周末分别测定血清总胆固醇和甘油三酯 ,并分别处死 7只兔取主动脉染色测定主动脉粥样硬化斑块面积。结果发现 ,与对照组相比 ,第8、12周末时动脉粥样硬化模型组血清总胆固醇和甘油三酯均显著增高 ,总胆固醇第 8周末为 14 .86± 4 .15mmol L ,第 12周末时为 18.8± 7.6 8mmol L ;甘油三酯第 8周末为 1.83± 0 .4 9mmol L ,第 12周末时为 2 .5 9± 0 .6 3mmol L。第8、12周末时对照组主动脉粥样硬化斑块面积均为零 ,而动脉粥样硬化模型组主动脉粥样硬化斑块面积分别为 35 .2 9%± 9.4 1%和 4 2 %± 9.6 9% ;辛伐他汀组和舒降之组血清总胆固醇和甘油三酯及主动脉粥样硬化斑块面积均显著低于同期动脉粥样硬化模型组 (P <0 .0 1) ,且该两组同期总胆固醇和甘油三酯及主动脉粥样硬化斑块面     

何首乌总甙抑制动脉粥样硬化病变形成

的　研究何首乌总甙对载脂蛋白E基因缺陷小鼠实验性动脉粥样硬化病变形成的保护作用。方法　将载脂蛋白E基因缺陷小鼠随机分为4组:何首乌总甙高剂量组[15 0mg/ (kg·d) ]、低剂量组[2 5mg/ (kg·d) ]、阿托伐他汀阳性药物组[5mg/ (kg·d) ]及空白对照组,给药第10周后全部处死,酶法检测四组血清脂质含量,图象分析法测定主动脉粥样硬化斑块面积和管腔面积,计算斑块面积与管腔面积的比值。结果　(1)何首乌总甙高、低剂量组及阳性药物组总胆固醇分别为6 4 9.3±72 .2mg/dL、6 32 .6±5 5 .1mg/dL和4 97.4±14 0 .8mg/dL ,均显著低于空白对照组(80 9.4±4 2 .6mg/dL ,P <0 .0 1) ;甘油三酯分别为12 6 .6±4 8.1mg/dL、14 5 .6±37.9mg/dL和172 .1±15 .7mg/dL ,均显著降低于空白对照组(2 5 3.3±4 2 .6mg/dL ,P <0 .0 1) ;而高密度脂蛋白胆固醇分别为117.1±14 .9mg/dL、113.5±2 3.3mg/dL和12 6 .7±12 .8mg/dL ,均显著高于空白对照组(6 7.3±10 .6mg/dL ,P <0 .0 1) ;治疗组间无显著性差异(P >0 .0 5 )。(2 )何首乌总甙高剂量组、低剂量组及阳性药物组载脂蛋白E基因缺陷小鼠主动脉粥样硬化病变减轻且动脉粥样硬化斑块面积/管腔面积比值分别为3.97%±0 .6 2 %、3.11%±0 .0 1%和0 .86 %±0 .0 7% ,均小于空     

糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2和9与斑块稳定的关系

目的　比较糖尿病患者与非糖尿病组患者动脉粥样硬化斑块内基质金属蛋白酶 2和基质金属蛋白酶 9表达的差异 ,初步探索基质金属蛋白酶 2和基质金属蛋白酶 9与糖尿病动脉粥样硬化斑块稳定的关系。方法　从2 3例糖尿病足截肢和 17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织块共 12 6块 ,分为糖尿病组 (74块 )和非糖尿病组 (5 2块 ) ,从中随机选取各 4 0个组织块 ,运用免疫组织化学染色法检测基质金属蛋白酶 2和 9在两组粥样硬化斑块中的表达。结果　糖尿病组抗基质金属蛋白酶 2、抗基质金属蛋白酶 9免疫沉积物主要集中在斑块核心周围 ,特别是在斑块的肩部和纤维帽。糖尿病组动脉斑块内抗基质金属蛋白酶 2免疫沉积物表达显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 6 90 14± 14 4 5 9和 5 70 0 4± 16 171,阳性面积百分比分别为 13.0 %± 2 .7%和 11.1%± 3.3% ) ;糖尿病组斑块内基质金属蛋白酶 9表达也显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 10 2 4 85± 2 0 4 31和 75 2 80± 1310 6 ,阳性面积百分比分别为 18.4 %± 3.6 %和 13.7%± 2 .3% )。结论　基质金属蛋白酶 2和 9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组。基质金属蛋白酶 2和 9在糖尿病动脉中表达增     

福辛普利对高脂诱发动脉粥样硬化血管内皮细胞黏附分子-1 mRNA表达的影响

目的利用高脂诱发的动脉粥样硬化模型观察了血管紧张素转换酶抑制剂福辛普利(fosinopril)的抗动脉粥样硬化作用.方法将建立动脉粥样硬化模型日本大耳白兔32只,随机分为三组对照组8只;高胆固醇组11只;福辛普利组13只.检测如下指标⑴计算主动脉粥样斑块面积.⑵测定血浆脂蛋白水平及低密度脂蛋白(LDL)氧化易感性.⑶RT-PCR检测组织中血管内皮细胞黏附分子(VCAM-1) mRNA表达的水平.结果福辛普利组和高脂组与对照组相比总胆固醇和甘油三酯水平明显升高,但二组间差异无显著性(P>0.05).福辛普利组动脉粥样斑块面积明显低于高胆固醇组[(26±5.4)% 比 (41±9.6)%,P<0.05]; 与高脂组比较福辛普利明显延长CuSO4诱导的LDL脂蛋白氧化反应的潜伏期(150 min 与240 min,P<0.001).福辛普利组主动脉VCAM-1/GAPDH mRNA比值低于高胆固醇组(0.90±0.35和1.40±0.51,P<0.05).福辛普利组明显降低了主动脉组织中VCAM-1的mRNA的表达.结论血管紧张素转换酶抑制剂福辛普利通过抑制低密度脂蛋白的氧化及黏附分子VCAM-1的表达延缓早期的动脉粥样硬化病变.     

高频体表超声检测急性冠状动脉综合征患者颈动脉结构及功能

应用高频体表超声观察急性冠状动脉综合征患者颈动脉结构及血管内皮功能的变化 ,探讨动脉粥样硬化结构和功能与急性冠状动脉综合征的关系。对 35例急性冠状动脉综合征患者检测了颈动脉粥样硬化斑块、内膜中膜厚度、肱动脉内皮功能的变化 ,并与 2 7例稳定型心绞痛及 31例正常对照组进行比较。结果发现 ,内膜中膜厚度和内皮依赖性血管舒张功能在急性冠状动脉综合征组 (分别为 0 .10± 0 .0 2和 3.98± 1.6 5 )和稳定型心绞痛组(分别为 0 .11± 0 .0 4和 4 .76± 2 .37)与对照组 (分别为 0 .0 7± 0 .0 1和 9.33± 3.4 7)有显著差异 (P <0 .0 5 ) ,斑块积分和斑块指数在急性冠状动脉综合征组 (分别为 4 .0 6± 2 .2 1和 3.14± 1.97)与稳定型心绞痛组 (分别为 4 .17± 1.76和3.2 1± 1.88)间无差异 (P >0 .0 5 ) ,急性冠状动脉综合征组颈动脉粥样硬化斑块以不稳定型为主。研究结果提示 ,外周血管超声检查可观察动脉粥样硬化病变 ,颈动脉结构及血管内皮功能与冠状动脉粥样硬化有关。     

银杏叶提取物对高脂饮食所致血管内皮功能损伤的保护及与对氧磷酶活性的关系

为探讨银杏叶提取物对高脂血症所致血管内皮功能损伤的保护作用及其机制 ,在大鼠高脂血症模型对比观察了银杏叶提取物和维生素E的作用。结果发现 ,大鼠高脂血症导致血管内皮依赖性舒张反应和非内皮依赖性舒张反应、血清一氧化氮浓度和对氧磷酶活性显著降低、血清丙二醛浓度显著升高。银杏叶提取物 [2 5mg (kg·d) ]或维生素E[10 0mg (kg·d) ]对高脂血症无明显抑制作用 (P >0 .0 5 ) ,但显著保护血管舒张功能和一氧化氮的血清浓度及对氧磷酶的活性 ,阻止了丙二醛的升高。在对照组、高脂组、银杏叶提取物和维生素E组 ,一氧化氮浓度(mmol L)分别为 5 .16± 1.3、3.35± 1.0 7、5 .0 5± 1.4 1和 4 .91± 1.6 5 (高脂组比对照组 ,P <0 .0 5 ;高脂组比银杏叶提取物和维生素E组 ,P <0 .0 5 ) ;内皮依赖性舒张反应分别为 95 .1%± 19.8%、4 7.1%± 15 .0 %、81.8%± 9.3%和 76 .2 %± 11.3% (高脂组比对照组 ,P <0 .0 1;高脂组比银杏叶提取物和维生素E组 ,P <0 .0 1) ;非内皮依赖性舒张反应分别为 98.2 %± 3.6 %、5 6 .7%± 7.9%、85 .8%± 7.2 %和 83.6 %± 4 .9% (高脂组比对照组 ,P <0 .0 1;高脂比银杏叶提取物和维生素E组 ,P <0 .0 1) ;对氧磷酶活性 (kU L)分别为 :18.0 %± 7.2 %、7.9%± 3.7%、16 .5 %     

血小板活化与脑梗死及颈动脉粥样硬化的相关性

探讨血小板活化程度与脑梗死及颈动脉粥样硬化的关系。用流式细胞术检测 73例动脉粥样硬化性脑梗死患者及 6 1例对照者全血血小板膜糖蛋白PAC 1和CD6 2P阳性率 ,同时行颈动脉彩色多谱勒超声检查。与对照组相比 ,脑梗死组PAC 1和CD6 2P阳性率 (颈动脉粥样硬化脑梗死组分别为 14 .13± 5 .75和 15 .80± 8.89,颈动脉正常脑梗死组分别为 11.70± 5 .32和 12 .36± 6 .4 9)均显著高于对照组 (颈动脉粥样硬化对照组分别为 7.78± 5 .17和7.5 5± 5 .2 8,颈动脉正常对照组分别为 4 .77± 3.71和 5 .0 5± 4 .0 1) (P <0 .0 1) ;不管在脑梗死组还是对照组中 ,颈动脉粥样硬化者PAC 1和CD6 2P阳性率显著高于颈动脉正常者 (P <0 .0 5 ) ,且以颈动脉粥样硬化脑梗死组最高。此结果提示 ,血小板活化程度与脑梗死、颈动脉粥样硬化二者均有关系 ,活化血小板在动脉粥样硬化性脑梗死患者发病中可能起着重要作用。     

茶色素对冠心病患者血浆总抗氧化能力和氧化型低密度脂蛋白水平的影响

为探讨茶色素对体内抗氧化状态的影响 ,观察了 6 5例冠心病患者口服茶色素后血浆总抗氧化能力和氧化型低密度脂蛋白水平的改变。采用分光光度计测定受检者血浆总抗氧化能力水平 ,采用酶标法测定血浆氧化型低密度脂蛋白水平。结果发现 ,服药前冠心病患者血浆总抗氧化能力水平低于正常对照组 (P <0 .0 1 ) ,血浆氧化型低密度脂蛋白基础水平高于正常对照组 (P <0 .0 1 ) ;与服药前相比 ,服药 4周后茶色素组和维生素E组病人的血浆总抗氧化能力水平升高 (P <0 .0 5 ) ,血浆氧化型低密度脂蛋白水平下降 (P <0 .0 5 ) ;服药 8周后 ,茶色素组和维生素E组病人血浆总抗氧化能力水平进一步升高 (P <0 .0 1 ) ,血浆氧化型低密度脂蛋白水平进一步下降 (P <0 .0 1 ) ;服药前茶色素组、维生素E组及安慰剂组 3组患者之间的血浆总抗氧化能力水平无统计学差异 (P >0 .0 5 )。以上提示 ,冠心病患者的抗氧化能力低下 ,茶色素具有明显的抗氧化作用 ,能抑制体内低密度脂蛋白的氧化 ,推测其对阻止动脉粥样硬化的进一步发展起到有益作用     

云芝多糖对实验性动脉粥样硬化家兔血浆氧化型低密度脂蛋白含量的影响

用本室制备的两株单克隆抗体比较了经与未经云芝多糖治疗的实验性动脉样粥样硬化家兔血浆氧化型低密度脂蛋白的含量。发生血浆氧化型低密度脂蛋白以低、中修饰度低密度脂蛋白为主，血浆氧化型低密度脂蛋白水平与主动脉粥样硬化斑块面积成正相关，云芝多糖能降低血浆氧化型低密度脂蛋白水平。提示利用单克隆抗体检测血浆氧化度，云芝多糖降低血浆氧化型低密度脂蛋白水平可能是其减轻动脉粥样硬化斑块面积的机理之一。     

The effect of vitamin E, probucol, and lovastatin on oxidative status and aortic fatty lesions in hyperlipidemic-diabetic hamsters

Diabetes mellitus is associated with an increased risk of premature atherosclerosis, which may be due in part to an increased rate of low density lipoprotein (LDL) oxidation. Previous studies have shown that vitamin E, probucol, and lovastatin can reduce the oxidative susceptibility of LDL in normoglycemic animal models; however, few studies have investigated this in conjunction with aortic fatty streak lesion formation in diabetic hyperlipidemic models. Forty-eight Syrian hamsters were made diabetic by intraperitoneal injection of low dose streptozotocin. Diabetic animals (12 animals/groups) received a high saturated fat and cholesterol diet for 12.5 weeks. At 2.5 week of dietary treatments, the diet was supplemented with either: (1) 500 IU/day vitamin E (D+E); (2) 1% probucol w/w of the diet (D+P); (3) 25 mg/kg lovastatin (D+L); or (4) diabetic control (D). An age-matched group of hamsters (n=6) receiving the same diet but not made diabetic (ND) was used as control. At the end of the study, aortic arch foam cell-rich fatty streak lesion, plasma glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), phospholipids, alpha-tocopherol, plasma lipid peroxide and the susceptibility of LDL to copper-catalyzed oxidation were determined. Diabetes increased plasma glucose, and when combined with an atherogenic diet resulted in a further increase of plasma lipids. Vitamin E, probucol, and lovastatin significantly reduced plasma TG in the diabetic hamsters fed the atherogenic diet. Vitamin E treatment increased TC, probucol reduced HDL-C without affecting TC; whereas lovastatin reduced TC and selectively decreased non-HDL-C, and significantly reduced fatty streak lesion formation in the aortic arch. While vitamin E and probucol were effective in reducing several indices of oxidative stress including plasma lipid peroxides, cholesterol oxidation products and in vitro LDL oxidation, they had no effect on fatty streak lesion formation. Our results indicate that the LDL in diabetic animals is more susceptible to oxidation than in non-diabetic hamsters and that not only vitamin E and probucol but also lovastatin provide antioxidant protection. It appears that in this combined model of diabetes and hypercholesterolemia, progression of fatty streak lesion formation is mainly associated with changes in TC and non-HDL-C as affected by lovastatin, and is less dependent on the extent of LDL oxidation, changes in plasma TG level and oxidative stress status.     

The effect of pharmacological doses of different antioxidants on oxidation parameters and atherogenesis in hyperlipidaemic rabbits

The oxidation hypothesis of atherosclerosis implies that antioxidants are able to inhibit lipoprotein oxidation in the arterial wall and thereby retard atherogenesis. Since most of the animal studies performed have used very high doses of antioxidants, it is to date unknown whether antioxidants are effective antiatherosclerotic agents when given in pharmacological doses. Here we addressed this question using homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits as an animal model of atherosclerosis. The rabbits were divided into four groups, each consisting of ten animals. They received either a standard diet or a diet containing 4.3 mg ubiquinone-10, or 4.3 mg vitamin E or 15 mg probucol/kg body weight daily. After 12 months, the extent of aortic atherosclerosis was assessed as the intima thickness, media thickness and intima-to-media ratio in 14 cross sections equally distributed over the whole aorta. To evaluate the antioxidant effects of the diet, lipophilic and hydrophilic antioxidants, lipids, fatty acids and plasma oxidizability were measured after 0, 3 and 6 months of feeding. We found that supplementation with probucol significantly decreased aortic intima-to-media ratio compared to controls. The antiatherosclerotic action of probucol was accompanied by its beneficial action on plasma oxidizability and some plasma antioxidants. No decrease in aortic atherosclerosis was measured in ubiquinone-10- and vitamin E-supplemented rabbits, despite the fact that both antioxidants decreased plasma oxidizability and ubiquinone-10 increased the plasma levels of antioxidants. Taken together, these data suggest that pharmacological doses of probucol retard atherogenesis in WHHL rabbits by an antioxidant mechanism, while ubiquinone-10 and vitamin E at these dosages are ineffective in this highly hyperlipidaemic model. The measurement of some oxidation-related parameters in plasma, such as lipophilic antioxidants, polyunsaturated fatty acids and lipoprotein oxidizability, may be useful in assessing the risk of atherogenesis in humans.     

Clinical trials of vitamin E in coronary artery disease: Is it time to reconsider the low-density lipoprotein oxidation hypothesis?

A wide range of structurally unrelated antioxidants inhibit atherosclerosis in animal models of hypercholesterolemia, implicating oxidation of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, most prospective, randomized trials of one proposed antioxidant, vitamin E, have failed to demonstrate any reduction in cardiovascular events in humans with established coronary artery disease. Recent clinical studies suggest that vitamin E is also ineffectual in the primary prevention of atherosclerosis. These observations have led many to question the relevance of LDL oxidation to the pathogenesis of human cardiovascular disease. However, vitamin E’s ineffectiveness in clinical trials might result from its failure to act as a physiologically relevant antioxidant. Indeed, vitamin E does not consistently inhibit atherosclerosis in hypercholesterolemic animals, and there is remarkably little evidence that clinically relevant doses of vitamin E result in inhibition of lipid peroxidation in vivo. Collectively, these observations indicate that there is little rationale for using vitamin E to prevent coronary artery disease in humans. They also strongly suggest that it will be critically important to establish that compounds with antioxidant activity in vitro actually prevent oxidative reactions in vivo before embarking on any new clinical trials.     

Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits

Consumption of a range of dietary antioxidants may be beneficial in protecting low density lipoprotein (LDL) against oxidative modification, as studies have demonstrated that antioxidants other than vitamin E may also function against oxidation of LDL in vitro. In the present study, the effect of polyphenol antioxidants on the susceptibility of LDL to copper-mediated oxidation was investigated after feeding semi-purified diets to 3 groups of New Zealand white (NZW) rabbits. All diets comprised 40% energy as fat with 17% energy as oleic acid. Dietary fatty acid compositions were identical. Oils with different polyphenol contents were used to provide the dietary source of oleic acid — refined olive oil, extra virgin olive oil and Trisun high oleic sunflower seed oil. Polyphenolic compounds (hydroxytyrosol and p-tyrosol) could only be detected in the extra virgin olive oil. Vitamin E was equalised in all diets. LDL oxidizability in vitro was determined by continuously monitoring the copper-induced formation of conjugated dienes after 6 weeks of experimental diet feeding. The lag phase before demonstrable oxidation occurred was significantly increased in the high polyphenol, extra virgin olive oil group (P < 0.05) when compared with combined results from the low polyphenol group (refined olive oil and Trisun), even though the LDL vitamin E concentration in the high polyphenol group was significantly lower. The rate of conjugated diene formation was not influenced by the presence of dietary polyphenols. Results demonstrate that antioxidants, possibly phenolic compounds which are present only in extra virgin olive oil, may contribute to the endogenous antioxidant capacity of LDL, resulting in an increased resistance to oxidation as determined in vitro.     

高脂血症患者LDL氧化易感性及调脂药物干预的影响

目的观察高脂血症对LDL氧化易感性的影响以及调脂药物干预后的改变.方法应用短程密度梯度超速离心分离血浆LDL,对11例高甘油三酯血症患者口服微粒化非诺贝特200 mg/d、10例高胆固醇血症患者口服普伐他汀10 mg/d治疗4周前后和6例正常人的LDL在体外以CuCl2诱导氧化,测定LDL开始氧化的迟滞期和氧化速率.结果 (1)LDL氧化的迟滞期,在高甘油三酯血症患者和高胆固醇血症患者均较正常组明显缩短(43.8±11.6,40.8±10.7 vs 70.5±14.6 min, P均<0.01).(2)LDL的氧化速率,在高甘油三酯血症患者和高胆固醇血症患者均较正常组明显增快(0.036±0.004,0.031±0.011 vs 0.020±0.011 O.D./min,P均<0.05).(3)高甘油三酯血症患者给微粒化非诺贝特治疗后LDL氧化的迟滞期显著延长(62.4±5.0 min,P<0.01),氧化速率明显减慢(0.031±0.003 O.D./min,P<0.05).(4)高胆固醇血症患者于普伐他汀治疗后LDL氧化的迟滞期明显延长(58.8±6.1 min,P<0.05),氧化速率无显著性变化(0.025±0.009 O.D./min,P>0.05).结论高甘油三酯血症患者和高胆固醇血症患者LDL氧化易感性增高,微粒化非诺贝特和普伐他汀能够降低高甘油三酯血症患者及高胆固醇血症患者LDL的氧化易感性.     

Susceptibility of low- and high-density lipoproteins from diabetic subjects to in vitro oxidative modification.

AIMS: To investigate the hypothesis that lipid peroxidation of both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) is important in the development of atherosclerosis. METHODS: We have investigated whether LDL and HDL from patients with Type 1 diabetes mellitus (DM, n = 16) and Type 2 DM (n = 15) is more susceptible to Cu2+ -induced lipid peroxidation than LDL and HDL from a similar number of nondiabetic controls matched for age, gender and serum cholesterol. RESULTS: The vitamin E content of LDL and HDL from both groups of diabetic patients was not significantly different from controls. The LDL from Type 2 diabetic patients and HDL from both diabetic groups were significantly richer in triglyceride than controls. Phospholipid was decreased in LDL from Type 2 diabetic patients and protein was decreased in HDL in Type 1 DM, but otherwise the composition of LDL and HDL in diabetic subjects was similar to controls. No significant differences were observed in the generation of conjugated dienes or lipid peroxides in either LDL or HDL when the two groups were compared with each other or with their respective controls. CONCLUSIONS: Increased lipid peroxidation occurring in vivo in diabetes is unlikely to be the result of increased susceptibility of lipoproteins to lipid peroxidation, but rather to increased generation of free radicals, to oxidation of lipids other than those present in serum lipoproteins or to decreases in antioxidant systems other than the fat-soluble antioxidants present in lipoproteins.     

A novel alkaloid antioxidant, Boldine and synthetic antioxidant, reduced form of RU486, inhibit the oxidation of LDL in-vitro and atherosclerosis in vivo in LDLR(-/-) mice

A corollary to the oxidation hypothesis of atherosclerosis is that the consumption of antioxidants is beneficial. However, the literature is divided in support of this conclusion. In this study, Boldine, an alkaloid of Peumus boldus and reduced form of RU486, was tested for their antioxidant potency both in, in vitro oxidation system and in mouse models. Boldine decreased the ex-vivo oxidation of low-density lipoprotein (LDL). Two different in vivo studies were performed to study the effect of these compounds on the atherosclerotic lesion formation in LDLR(-/-) mice. In study I, three groups of LDLR(-/-) mice (N = 12 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 and 3 were given 1mg of Boldine or Red RU per day for 12 weeks. In study II, two groups of LDLR(-/-) mice N = 10 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 was given 5mg of Boldine per day. The results indicated that there was a decrease in lesion formation reaching a 40% reduction due to Boldine and 45% reduction by Red RU compared to controls. The in vivo tolerance of Boldine in humans (has been used as an herbal medicine in other diseases) should make it an attractive alternative to Vitamin E.     

Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial.

We have conducted an intervention trial to assess the effects of antioxidants and B-group vitamins on the susceptibility of low-density lipoprotein (LDL) to oxidation. A total of 509 men aged 30-49 from a local workforce were screened for total plasma homocysteine. The 132 selected (homocysteine concentration > or = 8.34 mumol/l) men were randomly assigned, using a factorial design, to one of four groups receiving supplementation with B group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin), antioxidant vitamins (150 mg ascorbic acid, 67 mg alpha-tocopherol, 9 mg beta-carotene), B vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-week study. The lag time of LDL isolated ex vivo to oxidation (induced by 2 mumol/l cupric chloride) was increased in the two groups receiving antioxidants whether with (6.88 +/- 1.65 min) or without (8.51 +/- 1.77 min) B-vitamins, compared with placebo (-2.03 +/- 1.50) or B-vitamins alone (-3.34 +/- 1.08) (Mean +/- S.E., P < 0.001). Antibodies to malondialdehyde (MDA) modified LDL were also measured, but there were no significant changes in titers of these antibodies in any group of subjects whether receiving antioxidants or not. Contrast analysis showed that there was no interaction between antioxidants and B-group vitamins. This study indicates that while B-group vitamins lower plasma homocysteine they do not have an antioxidant effect. Thus B-group vitamins and antioxidants appear to have separate, independent effects in reducing cardiovascular risk.     

Dietary fatty acid composition influences the degree of human LDL oxidation, but has only minor effects on vascular tone in a bioassay system

BACKGROUND AND AIM: Oxidized LDL has been detected in atherosclerotic vessels and presumed to be one of the major risk factors in atherosclerosis and cardiovascular diseases. The aims of the present study were to clarify whether the oxidation degree of LDL influences arterial tone and whether different long-lasting dietary habits have effects on biological variables. METHODS AND RESULTS: The lag phase of LDL oxidation was shorter (117 +/- 6 min) in the fish diet group than in the vegetarian (153 +/- 5 min) or the control diet group (152 +/- 10 min). The rat mesenteric arterial rings, which were preincubated with LDL oxidized to 1-30%, from the vegetarian and the fish diet groups showed (p < 0.05) decreased NA-induced maximal contraction forces when compared to the control diet. The LDL oxidation degrees of 31-60% and 61-90% had no effect on NA- and KCl-induced maximal contraction forces when compared to native LDL, nor were there differences between the diet groups. Endothelium-dependent and independent relaxation responses behaved similarly in all groups and were independent of the degree of oxidation. CONCLUSIONS: Dietary habits change the fatty acid composition of LDL, but have only minor effects on the vasoactive properties of oxidized LDL.