Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised‐controlled trial

Diepeveen, S. H. A.; Verhoeven, G. W. H. E.; Palen, Job van der; Dikkeschei, L. D.; Tits, Lambertus J. van; Kolsters, G.; Offerman, Jjg; Bilo, Henk J. G.; Stalenhoef, Anton F. H.

doi:10.1111/j.1365-2796.2005.01484.x

Cited by 65 publications

(45 citation statements)

References 27 publications

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“…Anti-oxidative and anti-inflammatory actions are also major pleiotropic effects of statins (12). Several reports have shown that these actions of statins contribute to their renoprotective effects (5,30,31). In the present study, we also observed that pravastatin and rosuvastatin suppressed oxidative stress in db/db mice as well as these reports, whereas we could not detect the anti-inflammatory effect of statins in the kidneys of db/db mice.…”

Section: Discussionsupporting

confidence: 66%

Differential effect of statins on diabetic nephropathy in db/db mice

Tamura

Murayama²,

Minami³

et al. 2011

Int J Mol Med

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Abstract. Recent studies suggest a potential benefit of the lipid-lowering medication in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although statins have been widely used to lower serum cholesterol levels, the effect of these drugs on diabetic nephropathy has not been fully elucidated. In the present study, therefore, we addressed the role of different kinds of statins on diabetic nephropathy in db/db mice. Mice were fed with a standard diet with 0.005% (w/w) of pitavastatin, rosuvastatin, and pravastatin for 8 weeks starting from 8 weeks of age. The treatment with statins did not affect the food intake, body weight gain, adiposity, or blood pressure in db/db mice. Treatment with statins also had no effect on plasma lipid levels. In terms of the effect on albuminuria, pitavastatin and rosuvastatin reduced the urinary excretion of albumin by 60 and 40%, respectively, but not pravastatin, suggesting the effect of these two drugs on diabetic nephropathy. Furthermore, pitavastatin and rosuvastatin improved glomerular hypertrophy. All statins treatment improved insulin resistance. In addition, rosuvastatin and pravastatin treatment reduced oxidative stress measured by urinary 8-OHdG level, whereas the statins had no effect on the inflammatory response in the kidney of db/db mice. These results are not consistent with the renoprotective effect of statins. In conclusion, our data suggest that pitavastatin and rosuvastatin can improve diabetic nephropathy through the suppression of glomerular hypertrophy, independent of lipidlowering or anti-oxidative effects.

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Section: Discussionsupporting

confidence: 66%

Differential effect of statins on diabetic nephropathy in db/db mice

Tamura

Murayama²,

Minami³

et al. 2011

Int J Mol Med

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“…Although the SPACE study did not systematically measure levels of oxidative stress biomarkers in response to therapy, two subsequent reports have not found a significant effect of administering a-tocopherol, 800 IU/d, on plasma oxidized LDL or oxidative protein product concentration. 51,52 Similar to the SPACE study, a randomized trial comparing the antioxidant N-acetyl cysteine with placebo in dialysis Changes in F2 isoprostanes from baseline at month 6. Levels stayed relatively stable throughout the study for both groups.…”

Section: Discussionmentioning

confidence: 99%

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Himmelfarb

İkizler²,

Ellis³

et al. 2014

Journal of the American Society of Nephrology

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Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus a-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.

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“…For example, in patients treated with statins to reduce LDL cholesterol levels, interactions with simultaneously ingested vitamin E supplements may occur. A combined treatment with atorvastatin and α-TOH in stable, non-diabetic dialysis patients revealed a reduced in vitro oxidizability of LDL [241] . Podszun et al [242] found no interactions in guinea pigs fed with high-dose α-TOH (250 mg/kg diet)…”

Section: Interactions With Pharmaceuticsmentioning

confidence: 95%

“…The results depend, among others, on the evaluation of the data. When vitamin E serum levels were measured without any corrections most researchers found a decrease [241,[246][247][248][249][250] ; however, when vitamin E serum levels were normalized to plasma lipids, such as LDL cholesterol, total serum cholesterol or serum triglycerides, increased or unchanged ratios of vitamin E and serum lipids were observed [247,[249][250][251][252] . The underlying processes are still unclear but on the one hand, the decrease of circulating lipoproteins could directly cause reduced levels of vitamin E (in terms of absolute concentrations), whereas the ratio of vitamin E to serum lipids could at the same time be increased, as statins mostly decrease specific lipid fractions, namely LDL cholesterol and total cholesterol.…”

Section: Interactions With Pharmaceuticsmentioning

confidence: 97%

Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

168

138

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Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e. , when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a REVIEW

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Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised‐controlled trial

Cited by 65 publications

References 27 publications

Differential effect of statins on diabetic nephropathy in db/db mice

Differential effect of statins on diabetic nephropathy in db/db mice

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Complexity of vitamin E metabolism

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