Enhanced oxidizability of ubiquinol and <i>α</i>‐tocopherol during lovastatin treatment

Palomäki, Ari; Malminiemi, Kimmo; Metsä‐Ketelä, T.

doi:10.1016/s0014-5793(97)00609-1

Cited by 45 publications

(32 citation statements)

References 41 publications

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“…[27][28][29][30][31][32] Its level may be reduced by high-dose treatment with an HMG-CoA reductase inhibitor. 17,[33][34][35][36] In the present study, the LDL ubiquinol level decreased during the LT period. The lag time to conjugated-diene formation in ex vivo, isolated LDL was prolonged by ␣-tocopherol treatment (450 IU/d), regardless of concomitant treatment with lovastatin or placebo.…”

Section: Discussionmentioning

confidence: 70%

“…17,38,40,48 -52 These phenomena may be secondary to a greater decrease in the lipid moiety than that of the proteins in LDL. 17,49,53 Later phases of LDL oxidation can also be studied by using excessive, longlasting oxidation with other measures for LDL peroxidation, like the determination of thiobarbituric acid-reactive substances and trinitrobenzenesulfonic acid, 38 or LDL malondialdehyde, peroxides, and the total amount of conjugated dienes. 54 This kind of long-lasting oxidation may also lead not only to peroxidation of the lipids in the LDL particle but also to the degradation of its protein, like the inner part of apo B.…”

Section: Discussionmentioning

confidence: 99%

“…17 In brief, LDL was precipitated from EDTAplasma with heparin (Noparin, Novo Nordisk) and trisodium citrate (pH 5.0) in acid-washed Kimax glass tubes. 24 The lipid fraction of LDL was dissolved in chloroform/methanol (1:1, vol/vol).…”

Section: Metal Ion-independent Oxidation Of Ldlmentioning

confidence: 99%

“…16 We found earlier in hypercholesterolemic CHD patients not under any antioxidant treatment that the oxidation times of both LDL ubiquinol and LDL ␣-tocopherol were shortened significantly during lovastatin therapy. 17 This finding was associated with a shortened lag time to conjugated-diene formation, suggesting a diminished resistance of LDL particles to the early phase of oxidative stress. This oxidative resistance, at least partially, may be restored with ubiquinone supplementation.…”

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confidence: 96%

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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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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Metal Ion-independent Oxidation Of Ldlmentioning

confidence: 99%

mentioning

confidence: 96%

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

Palomäki

Malminiemi

et al. 1999

ATVB

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“…Mohr et al demonstrated that supplementation with CoQ10 resulted in an increased CoQ10 level within circulating human lipoproteins and in an increased resistance of LDL to incipient lipid peroxidation (29). Palomaki et al (30) reported that lovastatin therapy was associated with a significant decline in serum ubiquinol content and that there was an increased oxidizability of LDL in the lovastatin treated patients. In the present study the ubiquinol-10/LDL-cholesterol ratio showed no significant changes.…”

Section: Ubiquinol/ubiquinone Ratio and Antioxidantmentioning

confidence: 99%

Reduction of Serum Ubiquinol-10 and Ubiquinone-10 Levels by Atorvastatin in Hypercholesterolemic Patients

Mabuchi

Higashikata

Kawashiri

et al. 2005

JAT

107

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Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 ± ± ± ± ± 0.21 to 0.46 ± ± ± ± ± 0.10 µ µ µ µ µg/ml (p < 0.0001), and from 0.10 ± ± ± ± ± 0.06 to 0.06 ± ± ± ± ± 0.02 µ µ µ µ µg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion. J Atheroscler Thromb, 2005; 12: 111-119.

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Statins for the prevention of dementia

McGuinness

Craig

Bullock

et al. 2009

Cochrane Database of Systematic Reviews

204

185

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Enhanced oxidizability of ubiquinol and α‐tocopherol during lovastatin treatment

Cited by 45 publications

References 41 publications

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

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

Reduction of Serum Ubiquinol-10 and Ubiquinone-10 Levels by Atorvastatin in Hypercholesterolemic Patients

Statins for the prevention of dementia

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