Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome.
Abstract | CONTEXT: OBJECTIVE: METHODS: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. RESULTS:
Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P < .001 unless stated otherwise) lowered plasma cholesterol (-34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33% and -37%), sphingomyelin (-27% and -31%), monohexosylceramide (-40% and -47%), dihexosylceramide (-31% and -34%), and trihexosylceramide (-29% and -31%), and GM3 gangliosides (-29% and -26%), lysophosphatidylcholine (-32% and -37%), alkylphosphatidylcholine (-19% and -19%), phosphatidylcholine (-17% and -19%), alkenylphosphatidylcholine ( plasmalogen) (-20% and -22%), alkylphosphatidylethanolamine (-20%, P =.008 and -24%, P =.02), alkenylphosphatidylethanolamine ( plasmalogen) (-24%, P =.003 and -23%, P =.007), phosphatidylglycerol (-24%, P =.07, -31%, P =.046), and phosphatidylinositol (-34% and -40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine ( plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. CONCLUSIONS:
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Authors | Theodore W K Ng, Esther M M Ooi, Gerald F Watts, Dick C Chan, Jacquelyn M Weir, Peter J Meikle, P Hugh R Barrett |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 99
Issue 11
Pg. E2335-40
(Nov 2014)
ISSN: 1945-7197 [Electronic] United States |
PMID | 25140396
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fluorobenzenes
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Phospholipids
- Pyrimidines
- Sphingolipids
- Sulfonamides
- Rosuvastatin Calcium
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Topics |
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Double-Blind Method
- Fluorobenzenes
(administration & dosage, pharmacology)
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(administration & dosage, pharmacokinetics)
- Male
- Metabolic Syndrome
(blood)
- Middle Aged
- Phospholipids
(blood)
- Pyrimidines
(administration & dosage, pharmacology)
- Rosuvastatin Calcium
- Sphingolipids
(blood)
- Sulfonamides
(administration & dosage, pharmacology)
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