Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals

Leonhardt, W.; Kurktschiev, T.; Meißner, D.; Lattke, Peter; Abletshauser, C.; Weidinger, Gottfried; Jaross, W; Hanefeld, Markolf

doi:10.1007/s002280050338

Cited by 54 publications

(36 citation statements)

References 28 publications

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“…As a secondary analysis, the small number of dyslipidemic participants might contribute to the lack of power of the analysis as the larger decrease in plasma selenium in the statin group did not reach the statistical significance. Previous reports conducted on a short period and on a limited number of patients did not show any effect of statins on plasma selenium variations [38,39]. It can also be hypothesized that the response of plasma selenium to lipid lowering drugs, observed on cross-sectional analysis, reach a plateau and then is up-regulated by the changes in HDL-and LDL-cholesterol concentrations as suggested by the multiple linear regression models.…”

Section: Discussionmentioning

confidence: 85%

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients – The EVA study

Arnaud

Akbaraly

Hininger‐Favier

et al. 2009

Journal of Trace Elements in Medicine and Biology

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Section: Discussionmentioning

confidence: 85%

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients – The EVA study

Arnaud

Akbaraly

Hininger‐Favier

et al. 2009

Journal of Trace Elements in Medicine and Biology

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“…39 Fluvastatin has also been studied in a randomized, double-blind, parallel, placebo-controlled trial design, wherein the daily dose of 80 mg did not change the lag time significantly. 48 As in most of the earlier studies, 17,48 -52 oxidation tests were performed on frozen samples after the entire clinical phase had been completed. If some oxidation or conformational changes did occur in LDL, then lovastatin made LDL more vulnerable to minimal oxidation than placebo, because the conditions were the same for all samples and the treatment periods were balanced.…”

Section: Discussionmentioning

confidence: 99%

Effects of Lovastatin Therapy on Susceptibility of LDL to Oxidation During α-Tocopherol Supplementation

Palomäki

Malminiemi

et al. 1999

ATVB

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Abstract-A randomized, double-masked, crossover clinical trial was carried out to evaluate whether lovastatin therapy (60 mg daily) affects the initiation of oxidation of low density lipoprotein (LDL) in cardiac patients on ␣-tocopherol supplementation therapy (450 IU daily). Twenty-eight men with verified coronary heart disease and hypercholesterolemia received ␣-tocopherol with lovastatin or with dummy tablets in random order. The two 6-week, active-treatment periods were preceded by a washout period of at least 8 weeks. The oxidizability of LDL was determined by 2 methods ex vivo. The depletion times for LDL ubiquinol and LDL ␣-tocopherol were determined in timed samples taken during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated-diene formation. ␣-Tocopherol supplementation led to a 1.9-fold concentration of reduced ␣-tocopherol in LDL (PϽ0.0001) and to a 2.0-fold longer depletion time (PϽ0.0001) of ␣-tocopherol compared with determinations after the washout period. A 43% prolongation (PϽ0.0001) was seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced ␣-tocopherol in metal ion-independent oxidation by 44% and shortened the lag time of conjugated-diene formation in metal ion-dependent oxidation by 7%. In conclusion, ␣-tocopherol supplementation significantly increased the antioxidative capacity of LDL when measured ex vivo, which was partially abolished by concomitant lovastatin therapy. Key Words: ␣-tocopherol Ⅲ clinical trials Ⅲ lipid oxidation Ⅲ lovastatin Ⅲ ubiquinol H igh serum cholesterol concentrations and oxidation of LDL seem to play key roles in the pathogenesis of an atherosclerotic lesion. An effective means to treat hypercholesterolemic patients is through the use of statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA ) reductase inhibitors. They effectively decrease serum LDL cholesterol, increase HDL cholesterol levels slightly, and improve the prognosis of coronary heart disease (CHD) patients. 1,2 The prominent antioxidant in LDL is ␣-tocopherol, because in every LDL particle there are Ϸ6 to 8 molecules of ␣-tocopherol. 3-5 ␣-Tocopherol acts as a powerful antioxidant after the very early stage of LDL oxidation and especially during intense oxidative stress. 6 -8 However, under mild oxidation, ␣-tocopherol may act as a prooxidant, thus shifting the peroxidative insult from the surface to the inner part of the LDL particle. 8 -10 This event could be prevented by ubiquinol. 11 ␣-Tocopherol supplementation may have a significant role in the prevention of CHD. Retrospective data indicate an inverse relation between plasma concentrations of vitamin E and the risk of angina pectoris. 12 According to 1 prospective study, the serum ␣-tocopherol concentration may affect cardiac risk (ie, nonfatal myocardial infarction or cardiovascular death) in patients with coronary disease...

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“…In another study, fluvastatin at a dose of 40 mg/day administered for 8 weeks in 20 patients with hypercholesterolemia caused the similar reduction of conjugated dienes formed during ex vivo oxidation of LDL (Leonhardt et al 1997). Hussein et al (1997) demonstrated that treatment of hypercholesterolemic subjects with fluvastatin (40 mg/day) for 12 or 24 weeks reduced 2.2-azobis, 2-amidinopropane hydrochloride-(AAPH)-induced peroxidation of plasma lipids by 70 and 77%, respectively.…”

Section: Effect Of Statin Treatment On Ldl Oxidizabilitymentioning

confidence: 97%

“…Consistent with the antioxidant effect of statins, an increase in the GSH/GSSG ratio was noted, but it was not statistically significant. Fluvastatin administered at 40 mg/day for 8 weeks had no effect on α-tocopherol and retinol content in LDL isolated form hypercholesterolemic subjects (Leonhardt et al 1997). In another group of patients with hypercholesterolemia and hypertension, the same treatment regimen did not modify plasma reduced GSH (Hussein et al 2002).…”

Section: Statins and Antioxidant Systemmentioning

confidence: 98%

Statins and Modulation of Oxidative Stress

Bełtowski

2005

Toxicology Mechanisms and Methods

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Statins inhibit the activity of a rate-limiting enzyme in cholesterol biosynthesis, converting 3-hydroxy 3-methylglutaryl coenzyme A to mevalonate, and are widely used in the treatment of cardiovascular diseases. Statins decrease the synthesis of cholesterol and other nonsteroid isoprenoids originating from mevalonate, such as farnesyl- and geranylgeranylpyrophosphate, dolichol, and ubiquinone. Recent studies indicate that the beneficial effect of statins on cardiovascular risk also occurs in persons with normal plasma cholesterol because of the pleiotropic cholesterol-independent activities of statins. Among these effects, modulation of oxidative stress is one of the most important. Statins reduce the generation of reactive oxygen species by vascular NAD(P)H oxidase, inhibit the respiratory burst of phagocytes, antagonize the prooxidant effect of angiotensin II and endothelin-1, and increase the synthesis of vascular nitric oxide. Some statins and their metabolites posses direct free radical scavenging activity. The antioxidant effect of statins contributes to inhibition of atherogenesis, stabilization of atherosclerotic plaque, inhibition of myocardial hypertrophy and remodeling, and modulation of vascular tone. However, the prooxidant effect of statins resulting from the inhibition of ubiquinone synthesis has also been reported in some experimental models. This effect may contribute to side effects of statins, such as myopathy and hepatotoxicity.

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Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals

Abstract: Fluvastatin therapy had lipid-lowering and antioxidative effects.

Cited by 54 publications

References 28 publications

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients – The EVA study

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients – The EVA study

Effects of Lovastatin Therapy on Susceptibility of LDL to Oxidation During α-Tocopherol Supplementation

Statins and Modulation of Oxidative Stress

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