Decreased susceptibility to copper-induced oxidation of rat-lipoproteins after fibrate treatment: influence of fatty acid composition.

1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (39%). This effect was related to a significant reduction (67% for CFB and 56% for BFB) in the amount of circulating VLDL-protein. 3. Plasma total cholesterol was reduced by 28% and 45% in CFB- and BFB-treated animals, respectively, mainly by modification of the cholesteryl ester fraction. In contrast, GFB significantly increased total cholesterol (27%). No modification in the LDL protein or lipid content was introduced by fibrates, although GFB decreased the proportion of LDL-triglycerides, at the expense of an increase in total cholesterol. 4. The fatty acid species carried by VLDL and LDL were affected after fibrate treatment. In general, both particles showed an increase in monounsaturated fatty acids (MUFA) (18:1) and a decrease in polyunsaturated fatty acids (PUFA) species (18:2 n-6, 20:4 n-6, 18:3 n-3, 20:5 n-3). As a consequence, the ratio of PUFA/(SFA+MUFA) for the whole lipoproteins was markedly reduced. 5. The degree of copper-induced VLDL- and LDL-oxidation was assessed by means of the analysis of lysine content, thiobarbituric acid reactive substances (TBARS) production and conjugated dienes formation. Lipoproteins obtained from fibrate-treated rats were more resistant to the oxidative challenge. For each lipoprotein, BFB was the most effective drug, followed by CFB and GFB. 6. The observed antioxidant effect can be ascribed to two independent phenomena produced by fibrates: the reduction of the amount of substrate for the oxidation process due to their hypolipidemic activity, and the alteration in the type of fatty acids transported by the lipoproteins towards an enrichment in species resistant to the oxidation process. 7. As similar lipoprotein fatty acid changes have been reported after fibrate treatment in human subjects, an antioxidant effect of fibrates in human therapy, independent of their well known hypolipidaemic activity, should be expected.     

Effect of simvastatin on the oxidation of native and modified lipoproteins

Modified (oxidized) low-density lipoprotein (LDL) plays a significant role in atherosclerosis by accumulation in arteries. Also, glycated LDL, such as in diabetics, are increasing the risk for atherosclerosis, due to an increased oxidizability as compared to native LDL. For these reasons, the potential inhibition of such modifications is of clinical importance. We investigated the influence of simvastatin on oxidation of native and modified LDL as well as high-density lipoprotein (HDL), which plays a protective role in atherosclerosis. Quantitative assessment of the oxidation end-product malondialdehyde (MDA) revealed the highest inhibitory rate for HDL at concentrations of 1.6 microg/ml and 0.8 microg/ml by 30.3% and 20.4%, at 6 h and 4 h, respectively. At 24 h, the inhibition was still persisting amounting to 27.9% and 20.3%, respectively. For native LDL, we found less inhibition of oxidation at a concentration of 1.6 microg/ml amounting to 19.2% and 11.5%, for 4 h and 6 h, respectively. Similar effects were found at a concentration of 0.8 microg/ml. For modified, glycated LDL, the most pronounced effect was found at a concentration of 1.6 microg/ml amounting to 22.4% for the period of 2-24 h of oxidation. For glycoxidated LDL, the inhibition of oxidation was less expressed amounting to 10.1% for the period of 2-6 h at the same concentration. The influence of simvastatin on lag time (protection from oxidation) by diene conjugation was also investigated. At the highest concentration of simvastatin (1.6 microg/ml), we found a prolongation of lag time from 73 min to 99 min for native LDL, for glycoxidated LDL 60 min to 89 min and for HDL 54 min to 64 min. For glycated LDL, only a small decrease of lag time (66 min versus 71 min) at same concentration was observed. For glycated and glycoxidated LDL, we found a moderate increase in relative electrophoretic mobility (REM) by 2.0 and 2.3, respectively, but no changes in the presence of simvastatin were observed. These data show that simvastatin besides its lipid-lowering action has also significant antioxidative properties.     

一氧化氮阿司匹林(NCX-4016)体外抗氧化作用

目的：探讨一氧化氮阿司匹林（NCX-4016）的体外抗氧化低密度脂蛋白的效应.方法：健康成人空腹12 h新鲜混合静脉血,离心取血浆.采用密度梯度超速离心法分离低密度脂蛋白（LDL）,鉴定其纯度并检测其浓度.以Cu^2＋体外诱导LDL氧化,制备LDL体外氧化模型,采用紫外分光光度计于234nm监测LDL氧化过程中共轭二烯键（CD）的形成情况.将NCX-4016加入反应体系,观察药物对反应体系内形成动力曲线的影响以及对LDL氧化的作用,同时以硫代巴比妥酸反应活性物（TBRAS）测定诱导LDL氧化前后过氧化脂质生成量的影响.结果：NCX-4016能够降低CD的最大生成量、延长潜伏期,降低LDL氧化产物丙二醛（MDA）的含量,并具有浓度依赖效应关系（P＜0.05）.在相同浓度条件下NCX-4016的抗LDL氧化效应显著高于阿司匹林（P＜0.05）.结论：NCX-4016对Cu^2＋诱导的LDL的氧化具有明显抑制作用.     

Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats

1. In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2. Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3. In vitro, kolaviron (10-60 micromol/L) inhibited the Cu2+-induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 micromol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 micromol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 micromol/L) elicited a 53% increase in lag time, whereas 40 and 60 micromol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4. Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 micromol/L) had a significant chelating effect on Fe2+ (78%). 5. In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis.     

The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, β, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (− 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n−3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.     

Inhibition of lipoprotein lipid oxidation

According to the oxidative modification hypothesis, antioxidants that inhibit the oxidation of low-density lipoprotein (LDL) are expected to attenuate atherosclerosis, yet not all antioxidants that inhibit LDL oxidation in vitro inhibit disease in animal models of atherosclerosis. As with animal studies, a benefit with dietary supplements of antioxidants in general and vitamin E in particular was anticipated in humans, yet the overall outcome of large, randomized controlled studies has been disappointing. However, in recent years it has become clear that the role of vitamin E in LDL oxidation and the relationship between in vitro and in vivo inhibition of LDL oxidation are more complex than previously appreciated, and that oxidative events in addition to LDL oxidation in the extracellular space need to be considered in the context of an antioxidant as a therapeutic drug against atherosclerosis. This review focuses on some of these complexities, proposes a novel method to assess in vitro 'oxidizability' of lipoprotein lipids, and summarizes the present situation of development of antioxidant compounds as drugs against atherosclerosis and related cardiovascular disorders.     

Protective effects of leaf extract of Zanthoxylum ailanthoides on oxidation of low-density lipoprotein and accumulation of lipid in differentiated THP-1 cells

It has been reported that extracts of stem and leaf of Zanthoxylum ailanthoides (ZLE) possess antioxidative properties. However, the biological importance of the ZLE is not well known. In our preliminary study, it showed that ZLE prepared from 75% alcohol highly contains flavonoids (5.8%). By HPLC analysis, it shows that the ZLE consists of flavonoid glycosides including rutin and hyperoside. We investigate the effects of ZLE on the oxidation of low-density lipoprotein (LDL; d = 1.019–1.063 g/mL) and the uptake of lipid in macrophage. Firstly, we explored the effect of ZLE on the oxidation of LDL by employing copper (II) sulfate (CuSO₄) as an oxidative inducer. Oxidation was monitored by the formation of conjugated diene and thiobarbituric acid relative substances (TBARS), relative electrophoretic mobility (REM), and fragmentation of apolipoprotein B-100 (Apo B). Our data showed that ZLE reduced the oxidation properties of LDL induced by CuSO₄. In addition, ZLE inhibited lipid accumulation in differentiated THP-1 cells treated with ox-LDL involving decreasing the expression of scavenger receptors such as scavenger receptor class AI (SR-AI) and CD36, which belongs to the class B scavenger receptor (SR-B). These results demonstrate the protective effect of ZLE on LDL oxidation and lipid accumulation in macrophage.     

Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta

1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low-density lipoprotein (LDL) from oxidation. We functionally evaluated the anti-oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in the presence or absence of fluvastatin (10 micromol/L) for 4 h, the N-LDL was mildly oxidized by incubation with 5 micromol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were prepared. The level of thiobarbituric acid-reactive substances (TBARS) in Flu-OxLDL and OxLDL markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu-OxLDL or OxLDL. The degree of impairment was significantly less in Flu-OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 micromol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.     

Oxidized low-density lipoproteins accumulate in rat lung after experimental lung edema induced by alpha- naphthylthiourea (ANTU)

Oxidation of the low-density lipoprotein (LDL) results in the production of modified LDLs. Oxidation of LDL cholesterol plays a role on the pathogenesis of endothelial dysfunction. This study was designed to investigate the possible participation of the oxidative modification of low density lipoprotein in the lung edema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent on the lung endothelium. When ANTU injected intraperitoneally into rats (15 mg kg(-1)), it produced lung edema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. A significant lung edema was observed 4 h after intraperitoneally injection of alpha-naphthylthiourea when compared with olive oil-injected control rats. On microscopic examination of alpha-naphthylthiourea-treated rats were shown to have severe lung injury, while no change was observed in olive oil-treated control rats. While there were no staining in control lungs, positive oxidized low-density lipoproteins immune-fluorescent staining were observed in lung edema group. Our study showed that oxidized low-density lipoprotein (oxLDL) accumulated in ANTU-induced lung damage. This is the first study in which accumulation of oxLDL molecules in the intact lung tissue were shown by fluorescent immune-staining method in experimental lung edema. The potential role of oxLDL in this pathology are still under investigation.     

Effects of dehydroepiandrosterone on oleic acid accumulation in rat liver

The purpose of the present study was to determine whether dehydroepiandrosterone (DHEA) affects de novo fatty acid synthesis, oleic acid formation, fatty acid oxidation, and very low density lipoprotein (VLDL) secretion, in relation to the accumulation of lipid containing oleic acid, in rat liver. The rates of hepatic de novo synthesis of both fatty acid and monounsaturated fatty acid, determined by incorporation of 3H from 3H(2)O into fatty acid, were increased markedly when rats were fed a diet containing 0.5% (w/w) DHEA for 14 days. The treatment of rats with DHEA also enhanced the conversion of [14C]stearic acid into oleic acid in the liver in vivo. DHEA did not suppress fatty acid degradation in the liver. Namely, mitochondrial palmitic acid oxidation in liver homogenates and isolated hepatocytes was increased approximately 1.9- and 5-fold, respectively, in DHEA-treated rats. Peroxisomal palmitic acid oxidation in isolated hepatocytes from rats treated with DHEA, however, was not significantly different from that of the control, despite the fact that peroxisomal degradation of palmitic acid in the liver homogenates was increased markedly. The rate of hepatic VLDL secretion in DHEA-treated rats was decreased markedly. These results indicate that the elevation of the hepatic fatty acid content, especially oleic acid, by DHEA feeding is due to an increase in both de novo fatty acid synthesis and the formation of oleic acid and to a decrease in the rate of hepatic VLDL secretion. Mitochondrial and peroxisomal fatty acid degradation does not appear to play a significant role in the accumulation of hepatic lipids.     

4-吗啉乙腈盐酸盐的抗人低密度脂蛋白氧化作用

目的　观察 4 吗啉乙腈盐酸盐及其衍生物的抗氧化特性。方法　分别在铜离子和 2 ,2′ 盐酸脒基丙烷 (AAPH)催化的低密度脂蛋白 (LDL)氧化反应中加入 4 吗啉乙腈盐酸盐 ,以共轭二烯、丙二醛的生成和相对电泳迁移率作为测定指标 ,并比较 4 吗啉乙腈盐酸盐等系列化合物的抗氧化效果。结果　 4 吗啉乙腈盐酸盐可使LDL氧化反应的潜伏期明显延长 ,LDL中共轭二烯和脂质过氧化产物的生成明显减少 ,相对电泳迁移率下降 ,上述作用均随 4 吗啉乙腈盐酸盐浓度增加而进一步加强。结论　 4 吗啉乙腈盐酸盐具有抗人低密度脂蛋白氧化作用     

An n-3 PUFA-rich microalgal oil diet protects to a similar extent as a fish oil-rich diet against AOM-induced colonic aberrant crypt foci in F344 rats

The chemopreventive effects of high fat microalgal oil diet on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male Fischer 344 rats following 8 weeks of dietary treatment. These effects were compared to the effects of high fat fish oil and high fat corn oil diets to determine whether microalgal oil is a good alternative for fish oil regarding protection against colorectal cancer. Despite the difference in fatty acid composition and total amount of n-3 polyunsaturated fatty acids (PUFAs) between microalgal oil and fish oil, both these oils gave the same 50% reduction of AOM-induced ACF when compared to corn oil. To determine whether oxidative stress could play a role in the chemoprevention of colorectal cancer by n-3 PUFAs, feces and caecal content were examined using the TBA assay. The results showed that lipid peroxidation does occur in the gastrointestinal tract. As several lipid peroxidation products of n-3 PUFAs can induce phase II detoxifying enzymes by an EpRE-mediated pathway, the in vivo results suggest that this route may contribute to n-3 PUFA-mediated chemoprevention. All in all, n-3 PUFA-rich oil from microalgae is as good as fish oil regarding chemoprevention in the colon of the rat.     

北沙参的脂肪酸特征及产地差异性分析

目的 研究北沙参的脂肪酸特征,比较山东莱阳、河北安国、内蒙古赤峰等三个主产地的北沙参脂肪酸差异。方法 Bligh and Dyer法提取总脂;甲酯化后,利用气相色谱-质谱联用仪（GC-MS）分析;通过与脂肪酸标准品及NIST 11.0质谱数据库比对鉴定脂肪酸种类,采用面积归一法分别计算各成分的相对质量分数。结果 分别从山东莱阳、河北安国和内蒙古赤峰的北沙参药材中鉴定了17、17和18种脂肪酸;三个产地药材的优势脂肪酸种类一致,依次为C18:2 n-6c（亚油酸,49.22~63.96%）、C16:0（棕榈酸,17.43~25.33%）和C18:1 n-9c（油酸,13.85~19.44%）,均未检测到n-3型多不饱和脂肪酸（PUFA）。山东莱阳药材的多不饱和脂肪酸总量（PUFA）低于河北安国及内蒙古赤峰,但饱和脂肪酸（SFA）、 单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）三者比值最接近1:1:1。结论 不同产地北沙参的脂肪酸种类相近。亚油酸是北沙参含量优势脂肪酸,提示可以作为北沙参防治胆固醇代谢相关疾病的质量标志物候选分子。     

Valsartan therapy has additive anti-oxidative effect to that of fluvastatin therapy against low-density lipoprotein oxidation: studies in hypercholesterolemic and hypertensive patients

In hypercholesterolemic and hypertensive patients, an increased propensity of their low-density lipoprotein (LDL) to oxidative modification has been observed. Because oxidized LDL (ox-LDL) plays a major role in atherosclerosis, the current study analyzed the anti-oxidative effect of valsartan (an angiotensin II receptor antagonist) therapy in combination with fluvastatin therapy in these patients. Administration of 40 mg/d of fluvastatin for 2 months to seven patients resulted in significant reduction in plasma total and LDL cholesterol (by 24-28%). Valsartan administration (80 mg/d for an additional 2-month period) in combination with fluvastatin did not further affect plasma cholesterol levels. Fluvastatin therapy inhibited the susceptibility of LDL to copper ion-induced oxidation, as shown by prolongation of the lag time by 22% and by a reduction of thiobarbituric acid-reactive substances (TBARS) levels by 14%, as compared with the patient's LDL baseline oxidation. The addition of valsartan to fluvastatin resulted in a further 17% prolongation of the lag time and in an additional reduction of 21% in TBARS levels. In a parallel study, the LDL from eight patients who were first treated with 80 mg/d of valsartan for 2 months demonstrated reduced susceptibility to copper ion-induced oxidation, as observed by prolongation of lag time by 23% and reduction in TBARS levels by 19%, compared with the baseline values. The administration of 40 mg/d of fluvastatin for an additional 2 months in combination with valsartan, however, demonstrated no further inhibitory effect on LDL oxidation. The anti-oxidative properties of fluvastatin and valsartan against LDL oxidation were also demonstrated in vitro and the combination of both drugs was shown to have an additive effect. Valsartan therapy in hypercholesterolemic and hypertensive patients has an additive anti-oxidative effect to that of fluvastatin therapy. This may be related both to the anti-oxidative properties of valsartan and to the blocking of angiotensin II-induced oxidative stress.     

The Hypolipidemic Activity of l-N-3-Methylphthalimido-butan-3-semicarbazone in Rodents

l-N-(3-Methylphthalimido)butan-3-one semicarbazone demonstrated potent hypolipidemic activity in normal rats and mice and hyperlipidemic diet-induced mice. The compound decreased tissue lipid levels and increased the fecal excretion of cholesterol and triglycerides. After 2 weeks of administration, serum lipoprotein levels were modulated so that very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol concentrations were reduced and high-density lipoprotein (HDL) cholesterol concentrations were elevated to levels unprecedented by the cyclic imide derivatives previously tested. The VLDL triglyceride content was also reduced. Hepatic in vitro enzymatic studies demonstrated that the compound suppressed the activity of enzymes in the early synthesis of fatty acids and cholesterol and the regulatory enzymes for the de novo synthesis of triglycerides.     

丹酚酸-A体外对人血清低密度脂蛋白氧化修饰的抑制作用

目的研究丹酚酸-A(Sal-A)对人血清低密度脂蛋白(LDL)氧化修饰的抑制作用。方法用Cu²⁺体外诱导LDL过氧化,观察Sal-A对MDA,脂褐素和维生素E含量,氧化LDL电泳迁移率以及对LDL氧化过程中自由基的产生及Sal-A螯合Cu²⁺的作用。结果LDL经Cu²⁺诱导过氧化后,丙二醛和脂褐素的生成增加,维生素E含量下降,LDL电泳迁移速度加快,LDL氧化过程中自由基的生成增加。10^-6～10^-4 mol·L^-1 Sal-A可剂量依赖性地抑制上述改变,并且Sal-A能螯合Cu²⁺。结论丹酚酸-A可有效地抑制Cu²⁺诱导的人LDL氧化,该作用可能与其清除自由基及螯合铜离子的能力有关。     

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO₄ caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO₄ for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression. Received: 29 January 1999 / Accepted: 19 April 1999 / Published online: 22 June 1999     

Adriamycin causes hyperlipemia as a consequence of nephrotoxicity

Adriamycin induced hyperlipemia: its features and mechanism(s) in rats were investigated. Massive hyperlipemia occurred 14–21 days after a single dose of adriamycin (7.5 mg/kg i.v.). All lipoprotein fractions were affected. Mild but significant changes in tissues were observed (liver and intestine triglycerides and kidney phospholipids were reduced). Lipid synthesis and secretion was decreased, as shown by the Triton WR1339 test 7 days after treatment, but subsequently returned to normal. Mitochondrial oxidation of long-chain fatty acids was markedly reduced in kidney, and a slight reduction was also observed in heart. Lipoprotein lipase activity was reduced in adipose tissue. These results suggest that adriamycin hyperlipemia is due to reduced lipid storage and utilization. Carnitine did not counteract hyperlipemia and proteinuria after adriamycin. Analogies to hyperlipemia following puromycin aminonucleoside-induced nephrotoxicity are discussed.     

Reduction of oxidative stress and modulation of autoantibodies against modified low-density lipoprotein after rosuvastatin therapy

AIMS: To examine the effect of 24 weeks' rosuvastatin treatment on oxidative stress and changes in immune response to oxidized low-density lipoprotein (LDL). METHODS: This was an open-label study of patients in Austria receiving 10 or 40 mg rosuvastatin daily alternately during 12 and 24 weeks. Circulating concentrations of antibodies to malondialdehyde-oxidized LDL (MDA-LDL), both IgG and IgM type, to copper-oxidized LDL (Cu-OxLDL-IgG), concentrations of oxidized LDL complexed to IgG (OxLDL-IC) and markers of oxidative stress and systemic inflammation in subjects with plasma LDL cholesterol concentrations between 130 mg dl-1 and 250 mg dl-1 and triglycerides相似文献